ATR抑制剂VX-970对CPT诱导的结肠癌细胞生长的影响  

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

作　　者：吴锦欢 陈玉平 李磊 薛颖 李振鑫 乔海晅 袁建 WU Jin-huan;CHEN Yu-ping;LI Lei;XUE Ying;LI Zhen-xin;QIAO Hai-xuan;YUAN Jian(School of Biomedical Engineering and Technology,Tianjin Medical University,Tianjin 300070,China;Key Laboratory of An＇hythmias of the MinisttT of Education of China,East Hospital,Tongji University School of Medicine,Shanghai 200120,China)

机构地区：[1]天津医科大学生物医学工程与技术学院,天津300070 [2]同济大学附属东方医院,心率失常教育部重点实验室,上海200120

出　　处：《天津医科大学学报》2018年第5期376-380,384,共6页Journal of Tianjin Medical University

基　　金：国家自然科学基金重大研究计划(91749115)

摘　　要：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。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.

关 键 词：VX-970 喜树碱 凋亡 结肠癌细胞 生长 

分 类 号：R735.35[医药卫生—肿瘤]