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Publication Name
World Journal of Gastrointestinal Oncology
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1948-5204
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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

Basic Study
Copyright: ©Author(s) 2026.
World J Gastrointest Oncol. Sep 15, 2026; 18(9): 121282
Published online Sep 15, 2026. doi: 10.4251/wjgo.121282
Figure 1
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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.
Figure 2
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Figure 2 The effect of cyclin-dependent kinase 6 on the proliferation of gastrointestinal stromal tumor cells. The effect of cyclin-dependent kinase 6 inhibitors on the proliferation of T1, 882, and 430 cell lines: T1 vs T1 + palbociclib (P), T1 + ripretinib (Ri) vs T1 + Ri + P (P > 0.05), 882 vs 882 + P, 882 + Ri vs 882 + Ri + P (P > 0.05), 430 vs 430 + P, 430 + Ri vs 430 + Ri + P (P > 0.05). The effect of cyclin-dependent kinase 6 inhibitors on the proliferation of T1 resistance index (RI), 882RI, and 430RI cell lines: T1RI vs T1RI + P, T1RI + Ri vs T1RI + Ri + P (P < 0.05), 882RI vs 882RI + P, 882RI + Ri vs 882RI + Ri + P (P < 0.05) and 430RI vs 430RI + P, 430RI + Ri vs 430RI + Ri + P (P < 0.05). aP < 0.05. P: Palbociclib; Ri: Ripretinib; RI: Resistance index.
Figure 3
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Figure 3 The effect of cyclin-dependent kinase 6 on the migration of gastrointestinal stromal tumor cells. T1 vs T1 + ripretinib (Ri), T1 + palbociclib (P) vs T1 + Ri + P (P < 0.001), 882 vs 882 + Ri, 882 + P vs 882 + Ri + P (P < 0.001), 430 vs 430 + Ri, 430 + P vs 430 + Ri + P (P < 0.001). T1 vs T1 + P, T1 + Ri vs T1 + Ri + P (P > 0.05), 882 vs 882 + P, 882 + Ri vs 882 + Ri + P (P > 0.05), 430 vs 430 + P, 430 + Ri vs 430 + Ri + P (P > 0.05). T1 resistance index (RI) vs T1RI + P, T1RI + Ri vs T1RI + Ri + P (P > 0.05), 882RI vs 882RI + P, 882RI + Ri vs 882RI + Ri + P (P > 0.05), 430RI vs 430RI + P, 430RI + Ri vs 430RI + Ri + P (P > 0.05). aP < 0.001. Scale bar = 100 μm. P: Palbociclib; Ri: Ripretinib; RI: Resistance index.
Figure 4
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Figure 4 The effect of cyclin-dependent kinase 6 on the invasion of gastrointestinal stromal tumor cells. T1 vs T1 + ripretinib (Ri), T1 + palbociclib (P) vs T1 + Ri + P (P < 0.001), 882 vs 882 + Ri, 882 + P vs 882 + Ri + P (P < 0.001), 430 vs 430 + Ri, 430 + P vs 430 + Ri + P (P < 0.001). T1 vs T1 + P, T1 + Ri vs T1 + Ri + P (P > 0.05), 882 vs 882 + P, 882 + Ri vs 882 + Ri + P (P > 0.05), 430 vs 430 + P, 430 + Ri vs 430 + Ri + P (P > 0.05). T1 resistance index (RI) vs T1RI + P, T1RI + Ri vs T1RI + Ri + P (P > 0.05), 882RI vs 882RI + P, 882RI + Ri vs 882RI + Ri + P (P > 0.05), 430RI vs 430RI + P, 430RI + Ri vs 430RI + Ri + P (P > 0.05). aP < 0.05. Scale bar = 100 μm. P: Palbociclib; Ri: Ripretinib; RI: Resistance index.
Figure 5
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Figure 5 The effect of cyclin-dependent kinase 6 on the cell cycle of gastrointestinal stromal tumor cells. In the T1, 882, and 430 cell lines, cyclin-dependent kinase 6 inhibitors had no significant effect on the cell cycle. However, in the ripretinib-resistant cell lines T1 resistance index (RI), 882RI, and 430RI, cyclin-dependent kinase 6 inhibitors significantly increased the proportion of cells in the G1 phase. P: Palbociclib; Ri: Ripretinib; RI: Resistance index.
Figure 6
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Figure 6 The effect of cyclin-dependent kinase 6 on the apoptosis of gastrointestinal stromal tumor cells. In the T1, 882, and 430 cell lines, cyclin-dependent kinase 6 inhibitors had no significant effect on cell apoptosis. However, in the ripretinib-resistant cell lines T1 resistance index (RI), 882RI, and 430RI, cyclin-dependent kinase 6 inhibitors significantly increased the proportion of apoptotic cells. T1 vs T1 + ripretinib (Ri), T1 + palbociclib (P) vs T1 + Ri + P (P < 0.001), 882 vs 882 + Ri, 882 + P vs 882 + Ri + P (P < 0.001), 430 vs 430 + Ri, 430 + P vs 430 + Ri + P (P < 0.001). T1 vs T1 + P, T1 + Ri vs T1 + Ri + P (P > 0.05), 882 vs 882 + P, 882 + Ri vs 882 + Ri + P (P > 0.05), 430 vs 430 + P, 430 + Ri vs 430 + Ri + P (P > 0.05). T1RI vs T1RI + P, T1RI + Ri vs T1RI + Ri + P (P > 0.05), 882RI vs 882RI + P, 882RI + Ri vs 882RI + Ri + P (P > 0.05), 430RI vs 430RI + P, 430RI + Ri vs 430RI + Ri + P (P > 0.05). aP < 0.001. P: Palbociclib; Ri: Ripretinib; RI: Resistance index.
Figure 7
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Figure 7 Cyclin-dependent kinase 6 expression correlates with protein kinase B expression and activation. A: Protein levels in gastrointestinal stromal tumor cell lines, including cyclin-dependent kinase 6 (CDK6), protein kinase B (AKT) and phosphorylated-AKT; B: MRNA levels in gastrointestinal stromal tumor cell lines, including CDK6, AKT; C: In the ripretinib-resistant cell lines, both the protein and mRNA levels of CDK6 were significantly decreased in the group treated with the AKT inhibitor; D: Effects of CDK6 inhibitors on the expression of apoptosis-related proteins in ripretinib-resistant cells. aP < 0.05, bP < 0.001. CDK6: Cyclin-dependent kinase 6; AKT: Protein kinase B; p: Phosphorylated; GAPDH: Glyceraldehyde-3-phosphate dehydrogenase; Ri: Ripretinib; P: Palbociclib; RI: Resistance index; BAX: B-cell lymphoma-2-associated X protein; Bcl-2: B-cell lymphoma-2.
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