PMCID string | Title string | Sentences string |
|---|---|---|
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To further investigate whether the combination of β‐elemene and imatinib promotes the imatinib sensitivity in GIST‐882‐IR and GIST‐T1‐IR cells by inducing ferroptosis, we conducted high‐throughput RNA‐seq to compare the gene expression profile of imatinib and/or β‐elemene‐treated GIST‐T1‐IR cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Compared with cells treated with imatinib alone, the co‐treatment of β‐elemene and imatinib induced changes in the intracellular expression profile. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | KEGG pathway enrichment analysis and GSEA revealed that the DEGs after dual‐drug treatment were enriched in the ferroptosis pathway (Figure 3B,C). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The results suggested that β‐elemene could indeed cause ferroptosis in GIST cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | β‐elemene induces ferroptosis in imatinib‐resistant GIST cells. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Chemical structure of β‐elemene. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | B‐C) Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis and GSEA showed that genes involved in ferroptosis were significantly dysregulated under β‐elemene treatment. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The Fe levels detected by FerroOrange fluorescence probe in GIST‐882‐IR and GIST‐T1‐IR cells treated with DMSO, imatinib, β‐elemene or imatinib+β‐elemene for 24 h. (E) Quantification of relative fluorescence intensity of Fe levels by Image J. (F) The MDA levels detected in GIST‐882‐IR and GIST‐T1‐IR cells treated with ... |
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. (I) The ROS accumulation was detected using flow cytometry analysis and statistical histograms of positive cells in GIST‐882‐IR and GIST‐T1‐IR cells treated with DMSO, imatinib, β‐elemene or imatinib+β‐elemene for 24 h. (J) Representative ... |
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 | Important aspects of ferroptosis‐mediated cell death are characterised by ROS, Fe and lipid peroxides and MDA accumulation. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To verify this possibility, we assessed ROS, Fe and lipid peroxides and MDA levels in imatinib‐resistant cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | By immunofluorescence examination, a promoted FerroOrange fluorescence was recorded in the β‐elemene plus imatinib‐treated GIST cells, indicating that co‐treatment with β‐elemene and imatinib promoted the accumulation of Fe in GIST‐882‐IR and GIST‐T1‐IR cells (Figure 3D,E). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The lipid peroxidation level was determined by fluorescent probe BODIPY 581/591 C11. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | As expected, treatment with β‐elemene or imatinib alone had only a slight effect, but combined treatment with β‐elemene and imatinib significantly increased both the intracellular lipid peroxidation level and MDA level (Figure 3F–H). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The lipid ROS, a specific index of ferroptosis, was also examined, and our results showed a significant increase in ROS levels in GIST‐882‐IR and GIST‐T1‐IR cells after β‐elemene plus imatinib treatment (Figure 3I). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Moreover, we used a TEM to observe changes in the mitochondrial ultrastructure of the cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | As shown in Figure 3J, red arrows indicated that GIST‐T1‐IR co‐treated with imatinib and β‐elemene shrunken mitochondria with increased membrane densities, or disappeared mitochondrial cristae, which were characteristic morphological features of ferroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In conclusion, these results strongly suggest that the co‐treatment of β‐elemene and imatinib can induce ferroptosis in imatinib‐resistant GIST cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | To determine the synergistic antitumour effects of β‐elemene and imatinib in GIST, we evaluated the viability of GIST‐882‐IR and GIST‐T1‐IR cells by treating them with different concentrations of drug combinations for 48 h. Cell cytotoxicity was measured by CCK8 assay, and the CI was calculated according to the Chou–Ta... |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We calculated CI values for each combination treatment to assess whether the combination of β‐elemene and imatinib showed synergistic enhancement of cell cytotoxicity. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The CI values for β‐elemene and imatinib for GIST‐882‐IR (imatinib, 30 µM; β‐elemene, 40 µg/L) and GIST‐T1‐IR (imatinib, 20 nM; β‐elemene, 10 µg/L) were .65 and .005, respectively, at 48 h and were the greatest synergistic effects observed for the assessed drug concentrations (Figure 4B). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In addition, the combination of the two drugs induced a significant reduction in colony formation, compared with the use of each drug alone (Figure 4C,D). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In order to obtain objective quantification of cell death, we carried out a PI staining assay followed by flow cytometry. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The PI staining assay showed that a significant increase in the number of dead cells was observed in GIST‐882‐IR and GIST‐T1‐IR cells when exposed to β‐elemene in combination with imatinib (Figure 4E,F). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Further, the ferroptosis inhibitor, Fer‐1 markedly blocked the effects of the combination treatment on colony formation (Figure 4G,H) and cell viability (Figure 4I). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | These results show that β‐elemene and imatinib exhibit synergistic lethal effects through ferroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | β‐elemene promotes imatinib sensitivity in imatinib‐resistant GISTs through ferroptosis. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The interaction between imatinib and β‐elemene on cell cytotoxicity was examined by the median‐effect method of Chou–Talalay. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The dose and combination index of imatinib in combination with β‐elemene on GIST‐882‐IR and GIST‐T1‐IR cells was estimated by calculation of combination index (CI) values using Compusyn software. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The darker point indicates a stronger synergistic effect. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The fraction affected values indicate the percentage of cell inhibition, while the CI values indicate the effects of combination treatments. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Antitumour effects of imatinib and β‐elemene in GIST‐882‐IR and GIST‐T1‐IR cells after the indicated treatment 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 | Representative results of PI‐positive cells in IM‐exposed GIST‐882‐IR and GIST‐T1‐IR after the indicated treatment and quantitative analysis after the treatment for 48 h. (F) Statistical histogram of the flow cytometry cell death analysis. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Antitumour effects of GIST‐882‐IR and GIST‐T1‐IR cells treated with or without ferroptosis inhibitor Ferrostatin‐1 (Fer‐1) 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 of GIST‐882‐IR and GIST‐T1‐IR cells treated with or without ferroptosis inhibitor Fer‐1. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cell viability of GIST‐882‐IR and GIST‐T1‐IR cells treated with or without ferroptosis inhibitor Fer‐1. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Schematic description of the in vivo anticancer effect of combined treatment with β‐elemene and imatinib in the cell line‐based xenograft model. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Photograph and comparison of tumour sizes in the indicated groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Growth curve of GIST‐T1‐IR xenografts in the indicated groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The tumour weight of GIST‐T1‐IR xenografts in the indicated groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Representative images of IHC staining of MKI67/K‐67 in mouse tumours. |
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 | To assess whether our in vitro results could be reproduced in vivo, we generated a GIST CDX model from GIST‐T1‐IR cells (Figure 4J). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Consistent with our results in vitro, imatinib and β‐elemene exhibited synergistic effects in the CDX model. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Results show that both imatinib and β‐elemene alone were found to slightly reduce tumour growth, while combined treatment with imatinib and β‐elemene completely suppressed tumour growth in vivo (Figure 4K–M). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Combined treatment with imatinib and β‐elemene significantly reduced the growth rate of GIST tumours as shown by IHC staining (Figure 4N). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Taken together, these results show that imatinib and β‐elemene exhibit synergistic lethal effects through ferroptosis. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | In order to further investigate the relationship between the differential gene expression profile and ferroptosis in GIST, we analysed our RNA‐seq data and found that HMOX1 expression was significantly increased in dual‐drug‐treated cells (Figure 5A,B). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blot analysis showed that, compared with the control group and the single drug groups, the expression of HMOX1 in the dual drug groups increased significantly, while the expression of GPX4 decreased (Figure 5C). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Moreover, HMOX1 expression significantly decreased in the imatinib‐resistant GIST cells, compared to their parental cells (Figure 5D). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | β‐elemene induced ferroptosis in imatinib‐resistant GISTs through HMOX1. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Heatmap of the RNA‐seq analysis results for GIST‐T1‐IR cells treated with DMSO or β‐elemene. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Volcano plot of down‐regulated and upregulated for GIST‐T1‐IR cells treated with DMSO or β‐elemene. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis of HMOX1 and GPX4 expression in GIST cells treated with imatinib, β‐elemene or imatinib+β‐elemene. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis of HMOX1 expression in parental and imatinib‐resistant GIST cells. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blotting analysis of HMOX1 in GIST‐882‐IR and GIST‐T1‐IR cells transfected with HMOX1‐expressing plasmid. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | CCK‐8 assay of sensitivity to imatinib in HMOX1‐overexpressed GIST‐882‐IR and GIST‐T1‐IR cells versus control 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 | The colony formation assay of sensitivity to imatinib in HMOX1‐overexpressed GIST‐882‐IR and GIST‐T1‐IR cells versus control 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 | Western blot showing changes in HMOX1 expression in response to Hemin. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | I‐J) The colony formation assay and statistical histogram of GIST‐882‐IR and GIST‐T1‐IR cells treated with imatinib+β‐elemene with or without hemin. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cell death measurements by flow cytometry analysis in GIST‐882‐IR and GIST‐T1‐IR cells treated with imatinib+β‐elemene with or without hemin. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | L–M) The colony formation assay and statistical histogram of GIST‐882‐IR and GIST‐T1‐IR cells treated with imatinib+β‐elemene with or without zinc protoporphyrin‐9 (ZnPP). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cell death measurements by flow cytometry analysis in GIST‐882‐IR and GIST‐T1‐IR cells treated with imatinib+β‐elemene with or without ZnPP. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Photograph and comparison of tumour sizes in different groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Growth curve of GIST‐T1‐IR xenografts in the indicated groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The tumour weight of GIST‐T1‐IR xenografts in the indicated groups. |
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 | Overexpression of HMOX1 has been shown to exert pro‐oxidant effects and to induce ferroptosis. , |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | HMOX1 detoxifies heme into biliverdin, releasing carbon monoxide and Fe. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We first established stable HMOX1 overexpressing cells from the GIST‐882‐IR and GIST‐T1‐IR cells (Figure 5E). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The CCK‐8 and colon formation assay showed that HMOX1 overexpression significantly inhibited the proliferation of GIST‐882‐IR and GIST‐T1‐IR cells exposed to imatinib, and imatinib sensitivity could be reversed (Figure 5F,G). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Addition of hemin induced ferroptosis more rapidly when treated in combination with imatinib and β‐elemene (Figure 5H–K). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | However, treatment with 10 µmol/L ZnPP, a specific inhibitor of HMOX1, attenuated cell death induced by the combination treatment (Figure 5L–N). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Based on this finding, we tried to determine the therapeutic effect of the combination of these three drugs in vivo. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | We found that the antitumour activity of mice treated with imatinib, β‐elemene and 20 µM hemin was significantly increased, compared with those treated with the control group and with imatinib and β‐elemene groups. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | And ZnPP can attenuate the antitumour effects of the combination with imatinib and β‐elemene (Figure 5O–Q). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | These results further emphasise that HMOX1 plays an essential role in the ferroptosis in GIST cells, which is induced by β‐elemene. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | A high expression of HMOX1 in GIST cells treated with β‐elemene and imatinib is a key factor in ferroptosis activation. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | But the specific mechanism of HMOX1 high expression under β‐elemene treatment is still unclear. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Here, we conducted the TPP assay to identify the potential targets of β‐elemene and explore the mechanisms of regulating HMOX1 expression (Figure 6A). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | TPP is an emerging technique that identifies ligand‐induced shifts of thermal stability in a high‐throughput manner, making it a great tool for tracking drug targets in living cells. |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | As shown in Figure 6B and Table S3, we overall identified 6063 proteins, out of which 53 exhibited high confidence (FC > 1.5; p‐value < .05, CV < .1). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | KEGG pathway analysis showed that β‐elemene was associated with cell growth and death pathway and drug resistance: antineoplastic pathway, which is consistent to our research (Figure S3A). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Functional enrichment analysis revealed that β‐elemene was closely associated with methyltransferase activity, giving us clues to further investigate (Figure S3B). |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | β‐elemene targets N6AMT1 to promote imatinib sensitivity in imatinib‐resistant GIST cells via the nuclear factor erythroid 2‐related factor 2 (NRF2)/HMOX1 axis. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The workflow for cellular targets identification of β‐elemene in GIST‐T1‐IR by thermal proteome profiling (TPP). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Heatmap of differentially expressed protein in GIST‐T1‐IR cells between control and β‐elemene‐treated groups. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Venn diagram of β‐elemene target screening. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Volcano plot of cellular targets of β‐elemene by the TPP strategy. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blot analysis of NRF2 and HMOX1 in GIST cells with or without N6AMT1 knockdown by small interfering RNA (siRNA). ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Western blot analysis of NRF2 and HMOX1 in GIST cells with or without N6AMT1 overexpression. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | Cellular thermal shift assay demonstrated a stabilisation effect of N6AMT1 with β‐elemene. ( |
PMC12390768 | β‐elemene promotes ferroptosis to improve the sensitivity of imatinib in gastrointestinal stromal tumours by targeting N6AMT1 | The interaction between β‐elemene with N6AMT1 targeting Asp103 was predicted by molecular docking. ( |
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