PMCID string | Title string | Sentences string |
|---|---|---|
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The blots were then washed 3 times for 10 min with TBST (TBS with 0.1% Tween 20) and incubated with HRP-conjugated goat anti-rabbit or mouse IgG secondary antibodies (1:5000) for 1 h at room temperature. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The bands were visualized by incubating the blots with enhanced chemiluminescence (ECL, Yeasen) solution and were imaged by a Bio-Rad Imaging system detector. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Cells were treated with 100 nmol/L THZ1 for 24 h. Then, the cells were fixed with 4% paraformaldehyde for 10 min, permeabilized with 0.2% Triton X-100 (Beyotime) for 15 min, blocked with 3% BSA for 60 min, and incubated with anti-c-KIT antibody (1:400) overnight at 4 °C. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The cells were incubated with Alexa Fluor conjugate-anti-rabbit IgG (H + L) secondary antibody (1:1000) for 60 min in the dark and then with DAPI (Yeasen) for 5 min. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The mouse experiments were approved by the Institutional Review Boards of Zhongshan Hospital. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Female BALB/c nude mice (4 weeks old) were obtained from Shanghai Jiesijie Laboratory Animal Co., Ltd. GIST-T1 cells were mixed with Matrigel (BD Biosciences) at a ratio of 1:1 and were subcutaneously injected into BALB/c nude mice at 3 × 10 cells per mouse. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | When the tumours of all mice grew to be visible, the mice were randomly divided into two groups (n = 5). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Mice were treated with THZ1 (10 mg/kg) or PBS intraperitoneally every three days. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Tumour volume was measured every three days by using the formula: V = 1/2* length (mm) * width (mm). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The mice were sacrificed when the tumour volume in the control group reached approximately 500 mm. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The tumours were harvested, weighed and used for IHC. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The RNA sequencing service was supplied by Applied Protein Technology (Shanghai, China). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | In brief, GIST-T1 cells were treated with DMSO or THZ1 (100 nmol/L) for 6 h. Then, RNA was extracted in triplicate by using TRIzol Reagent (Yeasen). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Paired-end libraries were prepared using an ABclonal mRNA-seq Lib Prep Kit (ABclonal, China) following the manufacturer’s instructions. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Sequencing was performed with an Illumina NovaSeq 6000/MGISEQ-T7 instrument. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The ClusterProfiler R software package was used for Gene Ontology (GO) analysis . |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | When p < 0.05, the GO function was considered to be significantly enriched. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | All statistical analyses were performed with Prism 8.0 (GraphPad Software). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Continuous variables are presented as the mean ± standard deviation (SD). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A two-tailed Student’s t test was used to analyse the significance of differences between two groups, and one-way ANOVA was used for multiple groups. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Statically significant differences were considered when P < 0.05. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | To analyse the differential CDK expression in GISTs, we obtained publicly available transcriptomic data of GSE136755 from the Gene Expression Omnibus (GEO), which includes gene microarray data and clinicopathological information for 59 primary GIST tumour samples without preoperative imatinib treatment . |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The results showed that the mRNA levels of CDK4, CDK7 and CDK9 were relatively higher than those of the other CDKs for CDK1-CDK10 (Fig. 1A). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Next, we measured the mRNA levels of CDK4, CDK7 and CDK9 in different GIST risk groups. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | CDK7 was significantly elevated in the high-risk group compared with the very low-, low- and intermediate-risk groups (P < 0.05 Fig. 1B), while the mRNA levels of CDK4 and CDK9 did not increase with the risk category (Additional file 1).Fig. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | 1High CDK7 protein expression is associated with a poor prognosis of GIST. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Based on data from the GSE136755 dataset, the mRNA levels of CDK4, CDK7 and CDK9 were relatively higher than those of other CDKs for CDK1-10. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The mRNA level was calculated via GEO2R. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B CDK7 expression was significantly elevated in high-risk GISTs based on the data from GSE136755. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Representative scanned images of GIST samples with low or high CDK7 protein expression, as determined by IHC. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | D Kaplan–Meier survival curves with a risk table showing that high CDK7 protein expression was significantly positively related to poor recurrence-free survival in GIST patients (P = 0.044) High CDK7 protein expression is associated with a poor prognosis of GIST. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Based on data from the GSE136755 dataset, the mRNA levels of CDK4, CDK7 and CDK9 were relatively higher than those of other CDKs for CDK1-10. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The mRNA level was calculated via GEO2R. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B CDK7 expression was significantly elevated in high-risk GISTs based on the data from GSE136755. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Representative scanned images of GIST samples with low or high CDK7 protein expression, as determined by IHC. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | D Kaplan–Meier survival curves with a risk table showing that high CDK7 protein expression was significantly positively related to poor recurrence-free survival in GIST patients (P = 0.044) To further validate our findings at the protein level in GIST samples, we examined CDK7 protein expression in tissue microarrays (TMAs) of 181 GIST samples by immunohistochemistry (IHC). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Two researchers separately evaluated the staining level and divided the patients into high and low CDK7 expression groups (Fig. 1C). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | We focused on the relationships between the expression level of CDK7 and clinicopathological characteristics, including sex, age, tumour size, mitotic index and risk category (Table 1). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A significant correlation was found between elevated CDK7 expression, a higher mitotic index and a higher risk of GIST (P < 0.05), while no significant relationship was found between CDK7 expression and sex, age or tumour size. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Kaplan–Meier survival analysis demonstrated that high CDK7 expression was strongly correlated with reduced recurrence-free survival (RFS) (P = 0.044, HR = 1.924, CI = 1.005–3.684, Fig. 1D).Table 1Relationship between CDK7 expression and clinicopathological characteristics of GIST patientsFactorCDK7 expressionP valueLow (112)High (69)Age < 6058420.233 ≥ 605427Sex Male51360.385 Female6133Tumor site Stomach74410.374 Intestine, colorectal3427 Others41Tumor size (cm) 0–5.063350.725 5.1–10.03926 > 10108Mitotic index (per 50 HPFs)* 0–576310.002 > 53537Modified NIH criteria* Very low/low48180.011 Intermediate229 High4141*Two cases of mitotic index and modified NIH criteria were not accessible Relationship between CDK7 expression and clinicopathological characteristics of GIST patients *Two cases of mitotic index and modified NIH criteria were not accessible In summary, CDK7 was highly expressed in high-risk GISTs and may participate in GIST progression. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | To investigate the role of CDK7 in GIST cells, two independent siRNAs were transfected into GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The transfection efficacy was detected by western blotting (Fig. 2A). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | As shown in Fig. 2B and C, CDK7 knockdown significantly suppressed cell proliferation and colony formation in both GIST T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | We next assessed the effect of CDK7 knockdown on GIST cell cycle progression. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | We found that CDK7 knockdown resulted in marked cell cycle arrest at the G1/S phase (Fig. 2D). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | These results indicate that CDK7 may play an oncogenic role in GIST cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | We also found that the cell cycle-related protein cyclin D1, a regulator of the G0–G1 to S-phase transition, was significantly suppressed. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Additionally, γH2AX was significantly upregulated, suggesting increased DNA damage after CDK7 knockdown (Fig. 2E). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Taken together, these data demonstrated that CDK7 might be a promising treatment target for GISTs. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Fig. 2Knockdown of CDK7 decreases cell viability and proliferation and induces cell cycle arrest. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Immunoblotting analysis of CDK7 expression after targeting siRNA-mediated CDK7 knockdown in GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A nontargeting siRNA and two independent siRNAs (siRNA1 and siRNA2) are represented by siNC, siCDK7-1, and siCDK7-2. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B CCK-8 cell viability assay after CDK7 knockdown in GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Colony formation assays of GIST-T1 and GIST-882 cells after CDK7 knockdown. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | D Flow cytometry analysis was used to detect and analyse the cell cycle distribution after CDK7 knockdown. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | E Immunoblotting analysis of cyclin-D1, CDK4 and γH2AX expression after CDK7 knockdown Knockdown of CDK7 decreases cell viability and proliferation and induces cell cycle arrest. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Immunoblotting analysis of CDK7 expression after targeting siRNA-mediated CDK7 knockdown in GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A nontargeting siRNA and two independent siRNAs (siRNA1 and siRNA2) are represented by siNC, siCDK7-1, and siCDK7-2. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B CCK-8 cell viability assay after CDK7 knockdown in GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Colony formation assays of GIST-T1 and GIST-882 cells after CDK7 knockdown. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | D Flow cytometry analysis was used to detect and analyse the cell cycle distribution after CDK7 knockdown. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | E Immunoblotting analysis of cyclin-D1, CDK4 and γH2AX expression after CDK7 knockdown The CDK7 inhibitor THZ1 exerts antitumorigenic effects in various cancers. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | To evaluate the antitumour effects of THZ1 in GIST, GIST-T1 and GIST-882 cells were treated with THZ1 for 72 h and 144 h, respectively. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | As shown in Fig. 3A and B, THZ1 significantly suppressed the viability of GIST cells in a dose-dependent manner. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The IC50 values were 41 nmol/L and 183 nmol/L for GIST-T1 and GIST-882 cells, respectively. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | At concentrations as low as 25, 50, or 100 nmol/L, THZ1 potently reduced the viability of GIST-T1 and GIST-882 cells in a time-dependent manner (Fig. 3C).Fig. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | 3THZ1 suppresses the proliferation and induces the apoptosis of GIST cells in vitro. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Dose–response curves of GIST-T1 and GIST-882 cells after treatment with THZ1 for 72 h and 144 h, respectively. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Cell viability was assessed with the CCK-8 assay. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B Colony formation assays of GIST-T1 and GIST-882 cells treated with THZ1. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Time-response curves of GIST-T1 and GIST-882 cells upon treatment with THZ1 at concentrations as low as 25, 50, and 100 nmol/L. D Flow cytometry analysis in GIST cells treated with THZ1 at the indicated concentrations or vehicle. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | E Immunoblotting analysis of cleaved caspase 3 and cleaved PARP protein expression after THZ1 treatment for 24 h THZ1 suppresses the proliferation and induces the apoptosis of GIST cells in vitro. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Dose–response curves of GIST-T1 and GIST-882 cells after treatment with THZ1 for 72 h and 144 h, respectively. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Cell viability was assessed with the CCK-8 assay. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B Colony formation assays of GIST-T1 and GIST-882 cells treated with THZ1. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Time-response curves of GIST-T1 and GIST-882 cells upon treatment with THZ1 at concentrations as low as 25, 50, and 100 nmol/L. D Flow cytometry analysis in GIST cells treated with THZ1 at the indicated concentrations or vehicle. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | E Immunoblotting analysis of cleaved caspase 3 and cleaved PARP protein expression after THZ1 treatment for 24 h The extent of apoptosis was assessed after THZ1 treatment with flow cytometry analysis. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Annexin V/PI staining illustrated that the percentage of apoptotic cells significantly increased in a THZ1 dose-dependent manner (Fig. 3D, E). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Apoptosis-related proteins were also detected. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | As shown in Fig. 3F, the expression of cleaved PARP, cleaved caspase-3 and γH2AX was markedly increased in GIST-T1 and GIST-882 cells after THZ1 treatment. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Collectively, these results revealed that THZ1 could inhibit GIST cell proliferation and induce apoptosis. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The tumour inhibitory effect of THZ1 in vivo was assessed in a subcutaneous xenograft model of GIST-T1. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | As expected, the results showed that THZ1 treatment led to a profound reduction in tumour volume and weight, corroborating the tumour inhibition effect in vitro (Fig. 4A). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Notably, THZ1 treatment resulted in a significant reduction in tumour volume and weight (Fig. 4B, C). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Ki67 and cleaved-caspase 3 immunostaining assays of tumour samples showed that THZ1 treatment dramatically inhibited cell proliferation and promoted cell apoptosis (Fig. 4D). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Collectively, these results revealed that THZ1 exerts a potent antitumor effect on GIST cells in vivo. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Fig. 4THZ1 shows antineoplastic properties in vivo. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Images of subcutaneous tumours from the vehicle or THZ1 treatment groups (n = 5). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B, C. Tumour volume and weight of the subcutaneous tumour model. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | THZ1 treatment led to a significant reduction in tumour volume and weight. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Immunohistochemistry staining of Ki67 and cleaved caspase-3 in tissue sections from vehicle- or THZ1-treated subcutaneous tumours THZ1 shows antineoplastic properties in vivo. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | A Images of subcutaneous tumours from the vehicle or THZ1 treatment groups (n = 5). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | B, C. Tumour volume and weight of the subcutaneous tumour model. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | THZ1 treatment led to a significant reduction in tumour volume and weight. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | C Immunohistochemistry staining of Ki67 and cleaved caspase-3 in tissue sections from vehicle- or THZ1-treated subcutaneous tumours Furthermore, we assessed the potential tumour inhibition efficacy of THZ1 in combination with imatinib in GIST-T1 and GIST-882 cells. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Cells were treated with a series of different drug concentrations. |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | The synergistic antitumour effect was analysed by using CompuSyn software, and combination index (CI) values were calculated based on the drug combination principles proposed by Chou-Talalay . |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Our data revealed that single treatment with THZ1 or imatinib significantly suppressed GIST-T1 and GIST-882 cell viability (Fig. 5A). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | THZ1 had strong synergistic effects with imatinib in both GIST-T1 and GIST-882 cells, and there was an advantage of combination treatment (Fig. 5A–C). |
PMC9454178 | THZ1 targeting CDK7 suppresses c-KIT transcriptional activity in gastrointestinal stromal tumours | Immunoblotting analyses showed that combination treatment with THZ1 and imatinib led to more upregulation of cleaved caspase 3 and PARP than single agent treatment (Fig. 5D). |
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