PMCID string | Title string | Sentences string |
|---|---|---|
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The grid box was set to 30 × 30 × 30 Å, and the grid point distance was .05 nm. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The output docking conformation with the highest scoring was considered by us as the bound conformation, and finally PyMol 2.5.4 was used for visualisation. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | β‐elemene and biotin‐EDA(Biotin‐Ethylenediamine) were dissolved in N,N‐Dimethylformamide(DMF), followed by the addition of EDCI, HOBT and DMAP. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The reaction was conducted at room temperature (RT) for 15 h. Subsequently, purification was performed via HPLC (acetonitrile: water = 65%∼95%, .1% TFA, flow rate 20 mL/min, RT) to obtain β‐elemene‐biotin. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To evaluate the binding effect between β‐elemene and β‐elemene‐biotin for N6AMT1, the GIST cell lysates were preincubated with β‐elemene for 1 h, then incubated with 20 µM β‐elemene‐biotin for 1 hat 4°C. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The β‐elemene‐biotin complex was then captured using streptavidin magnetic beads for 1 h at 4°C, washed three times and finally analysed by western blot. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The GIST gene expression profiles GSE132542 was obtained from the publicly available Gene Expression Omnibus database (http://www.ncbi.nlm.nih.gov/geo/). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The GSE132542 dataset contained 29 samples, including 14 imatinib‐naïve and 15 imatinib‐resistant GISTs. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We then used the web‐based visualisation and inference toolbox(eVITTA, easy Visualization and Inference Toolbox for Transcriptome Analysis, https://tau.cmmt.ubc.ca/eVITTAL) for transcriptome and Gene set enrichment analysis (GSEA) . |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Enrichment results were considered significant where the p‐value < .05 and FDR < .25. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The cells were inoculated in petri dishes covered with a coverslip, treated according to the groups and collected, rinsed and fixed with 4% paraformaldehyde for 15 min, permeated with .5% Triton X‐100 for 20 min and sealed with goat serum for 30 min. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Then the diluted primary antibody (NRF2, Proteintech, 16396‐1‐AP) was added, and the cells were incubated at 4°C overnight. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | After the washing with PBST three times, Cy3‐labelled Sheep Anti‐Rabbit Fluorescent Secondary Antibody IgG (Wuhan Bode Bioengineering Co. Ltd., BA1032) was added and the cells were incubated at room temperature for 1 h in darkness. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | After washing with PBST three times, the cells were stained with DAPI (Beyotime, C1002) and sealed with an anti‐fluorescent quencher. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The images were taken under a fluorescence microscope (Olympus BX53 biological microscope). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | qMSP was used to determine the methylation levels of NRF2 promoter using TaqMan‐based technology in a Lightcycler LC480 system (Roche Applied Science). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Total DNAs underwent bisulfite conversion using the EZ DNA Methylation‐Lightning Automation Kit (Zymo Research) according to the manufacturer's instructions. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | CpG islands in the NRF2 and HMOX1 promoters were predicted, and primers for MSP were designed using MetPrimer online analyser. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The designed primers are listed in the Supporting Information (Table S2). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Amplification reactions were performed in triplicate in a total volume of 20 µL that contained 50 ng of bisulphite‐modified DNA, 600 nM forward and reverse primers, and 10 µL of QuantiTect 2 × SYBR Green PCR mix (Invitrogen, Inc.). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | PCR conditions were as follows: 95°C for 15 min, followed by 40 cycles of denaturing at 95°C for 30 s, annealing at 58°C for 30 s and elongation at 72°C for 30 s. Cycle threshold values were obtained for both the methylated‐specific (M) and unmethylated‐specific (U) primer sets, and percent methylation was calculated for each sample using the following formula: % methylation = 100/(1 + 2)%. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | GIST cell line‐based xenograft (CDX) and patient‐derived xenograft (PDX) models were performed in this study. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | 5‐6‐week‐old female BALB/c nude mice were purchased from the Vital River Laboratory Animal Technology Co., Ltd. All mice were housed in specific‐pathogen‐free conditions. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A total number of 4 × 10 GIST‐T1‐IR cells were injected subcutaneously into the left flank of mice. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | When the tumour was palpable, mice were randomly divided into indicated groups and treated with indicated drugs. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Vehicle (negative control) and imatinib were administered orally (25 mg/ kg), and β‐elemene (50 mg/ kg) was administered intraperitoneally once every 3 days. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In the due day, mice were sacrificed, and tumours were excised for analysis of their sizes and their weights. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The PDX models were initially generated using fresh tumour samples from patients with imatinib‐resistant GIST that were subcutaneously implanted into the dorsal flank of mice as the first generation (F0). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Once an appropriate volume was reached, the tumours were excised, divided into equal pieces and subcutaneously implanted into mice as the second generation (F1). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | When the tumour was palpable, mice were randomly divided into indicated groups and treated with IM or β‐elemene or their combination as previously described. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Tumour volumes were calculated every 3 days according to the formula volume = (length × width) × 1/ 2 as described in the previous study. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In the due day, mice were sacrificed, and tumours were excised for analysis of their sizes and their weights. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | All procedures, following the National Institutes of Health Guide for the Care and Use of Laboratory Animals (NIH Publications No. 8023, revised 1978), were approved by the Sun Yat‐sen University Animal Care and Use Committee (L102012022120C, Guangzhou, China). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The data were analysed by GraphPad Prism 9 software in this study. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | All the results were represented as mean ± standard deviation. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Comparisons were performed using unpaired Student's t‐test between the two groups. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Multiple group comparisons were performed by using one‐way ANOVA. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A p‐value of less than .05 is considered to be statistically significant. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To explore the mechanism of imatinib resistance in GIST, GSEA was performed to compare the gene microarray profiles in GIST samples. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | GSE 132542 dataset contains 29 samples, which are divided into two groups according to the sensitivity of imatinib: imatinib‐naïve (n = 14) and imatinib‐resistant (n = 15). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A heatmap showed DEGs (Figure 1A). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Gene ontology analysis of DEGs of imatinib‐resistant/imatinib‐naïve revealed a significant enrichment in negative regulation of cell death (Figure 1B,C). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Imatinib resistance is associated with ferroptosis activity in gastrointestinal stromal tumour (GIST). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Heatmap of differentially expressed genes (DEGs) in imatinib‐naïve and ‐resistant GISTs from the GSE132542 dataset. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Gene ontology analysis of DEGs between imatinib‐naïve and ‐resistant GISTs from the GSE132542 dataset (all absolute log2 fold change > .5, false discovery rate (FDR) < 10%). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Gene set enrichment analysis (GSEA) plots of negative regulation of cell death signalling pathway. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis of caspase‐3, cleaved caspase‐3, caspase7, cleaved caspase‐7, phosphorylated RIP1, total RIP1, phosphorylated RIP3, total RIP3, GSDME, cleaved GSDME, GSDMD, cleaved GSDMD, ferritin heavy chain (FTH1) and glutathione peroxidase 4 (GPX4), solute carrier family 7 member 11 (SLC7A11), FSP1 and dihydroorotate dehydrogenase (DHODH) expression in parental and imatinib‐resistant (IR) GIST‐882 cells treated with 882 20 µM imatinib for 24 h (for GIST‐882 and 20 nM for GIST‐T1, 24 h). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Vinculin was included as a loading control. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis of caspase‐3, cleaved caspase‐3, caspase7, cleaved caspase‐7, phosphorylated RIP1, total RIP1, phosphorylated RIP3, total RIP3, GSDME, cleaved GSDME, GSDMD, cleaved GSDMD, FTH1 and GPX4, SLC7A11, FSP1 and DHODH expression in parental and IR GIST‐T1 cells treated with 20 nM imatinib for 24 h. Vinculin was included as a loading control. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The expression of FTH1 and GPX4 in imatinib‐sensitive and imatinib‐resistant GIST specimens using immunohistochemistry (IHC) staining assay (Mann–Whitney U test). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Statistics of FTH1 expression in imatinib‐sensitive (n = 30) and imatinib‐resistant GIST specimens (n = 10) and percentage of GIST specimens with high or low FTH1 expression. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Statistics of GPX4 expression in imatinib‐sensitive (n = 30) and imatinib‐resistant GIST specimens (n = 10) and percentage of GIST specimens with high or low GPX4 expression. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis showing the protein levels of FTH1, GPX4, SLC7A11, FSP1 and DHODH in six GIST specimens, including three samples from patients with imatinib‐treated PD(Progressive Disease) and three samples from patients with imatinib‐treated PR(Partial Response). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Data represent the mean ± standard deviation (SD); *p < .05; **p < .01; ***p < .001. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | An unpaired t‐test was used unless otherwise stated. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To further investigate the relationship between the regulation of cell death and imatinib response in GISTs, imatinib‐resistant GIST‐882 and GIST‐T1 cells were established, and their imatinib‐resistant characteristics were confirmed by the IC50 of imatinib. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | As shown in Figure S1B,C (Supporting Information), the IC50 of imatinib was significantly higher in GIST‐882‐IR and GIST‐T1‐IR cells than the corresponding parental cells (36.08 ± 1.66 vs.15.65 ± 1.61 µM and 34.28 ± 12 vs.7.824 ± 2.35 nM, respectively). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To confirm the type of cell death programs that regulated imatinib resistance, we further investigated these common cell death pathways, including apoptosis, necroptosis, pyroptosis and ferroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We evaluated the levels of relevant markers at the molecular level in the imatinib‐resistant GIST cells and corresponding parental cells during imatinib treatment. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We found that well‐established ferroptosis markers were significantly upregulated, such as FTH1, GPX4, SLC7A11, S100 calcium binding protein A4 (FSP1) and DHODH (Figure 1D,E). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | For apoptosis, the results revealed no obvious effect on caspase‐3 and caspase‐7 in imatinib‐resistant cells, but activation of cleaved caspase‐3 and caspase‐7 was observed in parental cells with imatinib treatment. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | This result is consistent with the previous study. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Accordingly, the markers of necroptosis exhibited similar patterns. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We noted enhanced levels of phosphorylated RIPK1 and RIPK3 in GIST‐882‐IR but no obvious difference after imatinib treatment. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | There is no obvious difference between phosphorylated RIPK1 and RIPK3 in GIST‐T1 cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Next, we explored the impact of imatinib treatments on markers of pyroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | GSDMD and GSDME are the main executioners that form membrane pores under specific conditions. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The results revealed no obvious effect on the cleavage of GSDME and GSDMD (Figure 1D,E). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Altogether, these data indicate that imatinib resistance in GIST cells may be associated with the negative regulation of ferroptosis activity. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We also investigate the expression of ferroptosis‐relevant markers in clinical samples. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | IHC staining revealed that the expression of FTH1 and GPX4 in imatinib‐resistant GIST clinical samples was higher than that in imatinib‐sensitive samples. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Moreover, the proportion of FTH1 and GPX4 high expression in imatinib‐resistant GIST samples is greater than that in imatinib‐sensitive samples, confirmed by the quantification of IHC staining (Figure 1G,H). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Additionally, western blotting validates the expression of FTH1, GPX4, SLC7A11, FSP1 and DHODH in fresh surgical tumour tissues from three imatinib‐resistant patients compared with three imatinib‐sensitive patients receiving neoadjuvant imatinib therapy (Figure 1I). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Altogether, these data indicate that imatinib resistance in GIST cells may be associated with negative regulation of ferroptosis activity. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Previous researches have also highlighted the critical role of ferroptosis in the development of resistance to IM in GIST, , , and imatinib induces ferroptosis in GIST by promoting STUB1‐mediated GPX4 ubiquitination. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Here, we evaluated the sensitivity of GIST‐882‐IR and GIST‐T1‐IR to ferroptosis relative to their parental cells at the same concentration of imatinib treatment. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We found that the intracellular lipid peroxides, Fe and MDA of GIST‐882‐IR and GIST‐T1‐IR cells were significantly lower than those of the corresponding parental cell lines (Figure 2A–E). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | These results suggested that the ferroptosis activity is inhabited in GIST‐882‐IR and GIST‐T1‐IR cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Ferroptosis activity is suppressed in acquired imatinib‐resistant GIST cells and inducing ferroptosis can promote imatinib sensitivity. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Representative fluorescent images of lipid peroxidation detected by BODIPY (581/591) C11 probe in GIST‐882, GIST‐882‐IR, GIST‐T1 and GIST‐T1‐IR with or without treatment of imatinib for 24 h. Scale bar = 100 µm. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Quantification of relative fluorescence intensity of oxidised BODIPY by Image J. (C) The Fe levels detected by FerroOrange fluorescence probe in GIST‐882, GIST‐882‐IR, GIST‐T1 and GIST‐T1‐IR cells with or without treatment of imatinib. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Quantification of relative fluorescence intensity of Fe levels by Image J. (E) The malondialdehyde (MDA) levels detected in GIST‐882, GIST‐882‐IR, GIST‐T1 and GIST‐T1‐IR cells with or without treatment of imatinib. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cell viability of imatinib‐exposed GIST‐882‐IR and GIST‐T1‐IR pretreated with erastin and RAS‐selective lethal 3 (RSL3) or not was detected via CCK‐8 assay. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cell death measurements were taken using flow cytometry analysis and statistical histograms of propidium iodide (PI)‐positive cells in IM‐exposed GIST‐882‐IR and GIST‐T1‐IR, pretreated with erastin and RSL3. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Statistical analysis of the cell death. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | All experiments were performed in triplicate, and relative colony numbers are shown as means ± SD. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Antitumour effects of imatinib in imatinib‐exposed GIST‐882‐IR and GIST‐T1‐IR pretreated with erastin and RSL3 or not were evaluated by colony formation assay. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Statistical analysis of the colony formation assay. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | All experiments were performed in triplicate. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Data represent the mean ± SD; *p < .05; **p < .01; ***p < .001. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | An unpaired t‐test was used unless otherwise stated. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A growing number of evidence indicates that the induction of ferroptosis can inhibit tumour growth and overcome drug resistance. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Here, we tested whether the pre‐treatment with ferroptosis inducer erastin and RSL3 can enhance the sensitivity of GIST‐882‐IR and GIST‐T1‐IR cells to imatinib. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Before treating cells with imatinib, we pretreated cells with erastin (1 µM) and RSL3 (.5 µM) for 6 h. This pretreatment produced no increase in cell death in GIST cells (Figure S2A,B). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | As shown in Figure 2F, pretreatment of erastin and RSL3 promoted the cytotoxic and inhibitory effects of imatinib on GIST‐882‐IR and GIST‐T1‐IR cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Consistently, colony formation (Figure 2G,H) and cell death assay (Figure 2I,J) showed that pretreatment of erastin and RSL3 significantly increased the sensitivity of imatinib in GIST‐882‐IR and GIST‐T1‐IR cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Taken together, the above findings indicated that inducing ferroptosis can promote imatinib sensitivity in imatinib‐resistant GIST cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | This led us to speculate that ferroptosis could be a strategy for susceptibility to imatinib‐based chemotherapy. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A previous study demonstrated that β‐elemene can induce ferroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We hypothesise that β‐elemene may also enhance the sensitivity of imatinib by inducing ferroptosis. |
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