Targeting cyclin-dependent kinase 6 partially reverses drug resistance in ripretinib-resistant gastrointestinal stromal tumor cells in vitro

Figure 1 In ripretinib-resistant cell lines, cyclin-dependent kinase 6 expression was significantly elevated at both the mRNA and protein levels. A: Detection of differentially expressed genes between drug-resistant cell lines and their parental drug-sensitive counterparts. T1 resistance index (RI) vs T1, 882RI vs 882 and 430RI vs 430; B: Detection of differentially expressed proteins between drug-resistant cell lines and their parental drug-sensitive counterparts. T1RI vs T1, 882RI vs 882 and 430RI vs 430; C: Co-expression analysis of transcriptomic and proteomic profiles. T1RI vs T1, 882RI vs 882 and 430RI vs 430; D: The quantitative polymerase chain reaction results demonstrated that the mRNA level of cyclin-dependent kinase 6 was significantly elevated in the ripretinib-resistant group. T1RI vs T1 (2.90 ± 0.311, P < 0.01), 882RI vs 882 (6.15 ± 0.56, P < 0.01) and 430RI vs 430 (2.67 ± 0.04, P < 0.01); E: The western blot results demonstrated that the protein level of cyclin-dependent kinase 6 was significantly elevated in the ripretinib-resistant group. T1RI vs T1 (1.55 ± 0.08, P < 0.01), 882RI vs 882 (1.37 ± 0.10, P < 0.01) and 430RI vs 430 (5.03 ± 0.48, P < 0.01). ^aP < 0.01. RI: Resistance index; DEP: Differentially expressed protein; NDEG: Non-differentially expressed gene; NDEP: Non-differentially expressed protein; DEG: Differentially expressed gene; CDK6: Cyclin-dependent kinase 6; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase.