ATR抑制剂VX-970对CPT诱导的结肠癌细胞生长的影响

目的:探讨ATR特异抑制剂VX-970对喜树碱抑制的结肠癌细胞HCT-116生长，促进结肠癌细胞HCT-116凋亡的影响。方法:采用克隆形成、MTS、流式细胞术等实验分别检测单独使用VX-970，CPT以及联合VX-970和CPT用药处理对细胞生长、细胞周期及凋亡等影响，蛋白免疫印迹检测DNA损伤关键蛋白p-ATR，p-Chk1，γH2AX等的表达。结果:VX-970增强CPT对HCT-116细胞生长和增殖的抑制作用，促进细胞凋亡和减弱细胞周期G2/M期的阻滞。结论:VX-970能显著增强CPT抑制HCT-116细胞生长，诱导细胞凋亡和提高细胞对CPT药物的敏感性。

Effect of ATR inhibitor VX-970 on the growth of colorectal cancer cell induced by CPT

Objective: To investigate the effect of VX-970, an ATR specific inhibitor, on growth and apoptosis induced by CPT in colorectal cancer cells. Methods: Upon absence or presence of VX970 in CPT treatment for colorectal cancer cells, cell survival, proliferation, cell cycle and apoptosis were detected by colony forming, MTS and cell flow cytometry; the expression of DNA damage response key proteins(p-ATR, p-Chk1, γH2AX) was detected by Western blot. Results: VX-970 enhanced the effect of CPT on inhibiting proliferation, promoted cell apoptosis and induced cell cycle G2/M phase arrest. Conclusion: Combining CPT with VX-970 could significantly inhibit the growth and apoptosis and sensitize human colorectal cancer cells to CPT.