ATM信号通路抑制剂ETP46464对替莫唑胺治疗脑胶质瘤化疗的增敏作用  

The chemosensitive effect of the ATM signal pathway inhibitor ETP46464 for temozolomide in brain glioma treatment

作　　者：陈欢欢[1] 蔡炜嵩[1] Chen Huanhuan;Cai Weisong(The Second Department of Oneology,Shengjing Hospital of China Medical University,Liaoning Shenyang 110004,China)

机构地区：[1]中国医科大学附属盛京医院第二肿瘤内科病房,辽宁沈阳110004

出　　处：《现代肿瘤医学》2018年第14期2168-2172,共5页Journal of Modern Oncology

基　　金：辽宁省科学技术计划项目(编号:201602812)

摘　　要：目的:研究ATM信号通路抑制剂ETP46464对替莫唑胺(temozolomide,TMZ)治疗脑胶质瘤(glioma)的化疗增敏作用。方法:CCK-8法测定细胞生存曲线;流式细胞仪检测细胞凋亡;Western blot检测凋亡蛋白表达。结果:CCK-8结果显示:TMZ单药组与对照组相比较,随着TMZ药物浓度的增加,光密度(OD)值降低,细胞存活率下降,且均低于对照组;TMZ联合ETP46464组与相同浓度TMZ单药组相比较,细胞存活率随TMZ浓度的增加而降低,且低于相同浓度TMZ单独作用下的细胞。流式检测细胞凋亡结果显示:相同浓度TMZ的条件下,TMZ联合ETP46464组脑胶质瘤U87细胞的凋亡率明显高于TMZ单药组;相同浓度ETP46464(0或10μmol/L)的条件下,随TMZ浓度的增加,细胞凋亡率增加,结果有统计学差异。Western blot结果显示:TMZ单药组磷酸化Chk2(p Chk2)表达高于TMZ联合ETP46464组磷酸化Chk2的表达。结论:ATM信号通路抑制剂ETP46464可能通过阻断磷酸化Chk2的表达,阻断ATM信号通路,从而阻止脑胶质瘤细胞化疗所致DNA损伤的修复,在替莫唑胺治疗脑胶质瘤中达到化疗增敏的作用,提高临床脑胶质瘤化疗有效率。Objective： Study of ATM signaling pathway inhibitor in the chemotherapy sensitization effect of temozolomide in brain glioma treatment. Methods： CCK-8 detects the cell survival curves. The flow cytometry detects the cell apoptosis. Western blot detects the expression of apoptosis protein. Results： CCK-8 result showed： Compare the TMZ single drug group with the control group,with the increase of TMZ concentration,cell apoptosis increased either while the OD values decreased which means the cell survival rate decreased and lower than the control group. Compare the TMZ combined with ETP46464 group with the TMZ single drug group,with the increase of TMZ concentration,the cell viability decreased and lower than the tumor cells in the same TMZ concentration of the TMZ single drug group. The result of the flow cytometry detects the cell apoptosis ： Under the same concentration of TMZ,the apoptosis rate of the brain glioma U87 cells in TMZ combined with ETP46464 group was significantly higher than that in the TMZ single drug group. Under the same concentration ETP46464（ 0 or 10 μmol/L）,the apoptosis rate increased with the increase of TMZ concentration. The results were statistically significant. Result of the Western blot： The expression of p Chk2 in TMZ single drug group was higher than that in TMZ combined with ETP46464 group. Conclusion： ATM signal pathway inhibitor ETP46464 can block the ATM pathway by block the expression of phosphorated Chk2,and stop DNA damage repair. Treatment with temozolomide combain with ETP46464 in glioblastoma multiforme can achieve chemotherapy sensitization effect,and increase the chemotherapy effective rate.

关 键 词：脑胶质瘤 替莫唑胺 ATM信号通路 化疗增敏 

分 类 号：R739.41[医药卫生—肿瘤]