顺铂加重乳腺癌MCF-7细胞DNA损伤促凋亡的研究  

Study of cisplatin aggravating DNA damage and causing a high apoptosis rate on breast cancer MCF-7 cells

作　　者：袁立明[1] 马楠[2] 曹交欢 文艺[1] 刘向光[1] 周纤纤 匡淑雯 陶晓军[1] 曾赵军[2] 

机构地区：[1]湖南师范大学医学院药物工程实验室,湖南长沙410013 [2]中南大学湘雅医学院分子生物学研究中心,湖南长沙410078

出　　处：《中国药理学通报》2017年第3期334-337,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30600753;81172154);湖南省自然科学基金面上项目(No 2016JJ2088);湖南省教育厅资助项目(No 13C541);湖南省中医药管理局资助项目(No 2015123)

摘　　要：目的顺铂(DDP)为广谱抗癌药物,本研究探讨其对MCF-7乳腺癌细胞DNA损伤的作用,并研究其引起细胞凋亡的机制。方法采用DDP(0、2、4、6、8、10 mg·L^(-1))处理乳腺癌MCF-7细胞48 h,MTT法检测顺铂对细胞活性的抑制作用,并计算IC_(50);Western blot检测DNA断裂形成的标志分子γ-H2AX及直接感受DNA双链断裂(DSBs)的分子ATM、细胞凋亡信号分子cleaved caspase-3及凋亡相关的蛋白钙蛋白酶calpain的表达。结果 DDP呈浓度依赖性抑制细胞MCF-7活性,IC_(50)为7.57 mg·L^(-1);与对照组(未采用顺铂处理)相比,顺铂处理组MCF-7细胞内γ-H2AX、ATM、cleaved caspase-3、calpain的表达量增多。结论 DDP可抑制乳腺癌MCF-7细胞的活性,其机制与促进MCF-7细胞凋亡,诱导DNA双链断裂,上调促凋亡相关蛋白有关。Aim Toinvestigatethemechanismsof DNA damage of cisplatin（DDP）,a broad spectrum an-ticancer drug on breast cancer MCF-7 cells and to stud-y the mechanism of apoptosis induced by DDP.Meth-ods MCF-7cellsweretreatedbyDDP（0,2,4,6,8, 10 mg·L-1 ）for 48 h.MTT assay was used to detect the inhibitory effect of DDP on MCF-7 cells,and IC50 value was calculated.Western blot was adopted to de-tect the expression ofγ-H2AX,which was the marker of DNA double stranded breaks（DSBs）and ATM（sen-sory molecules of DSBs ）,the apoptotic signal trans-duction molecule cleaved caspase-3 ,and the proteins associatedwithapoptosis：calpain.Results DDPin-hibited MCF-7 cell activity in a concentration-depend-ent manner and IC50 was 7. 57 mg·L-1 .In contrast to the control group （without DDP treatment）,MCF-7 cells with DDP treatment group expressed more γ-H2AX,ATM,cleaved caspase-3 and calpain.Conclu-sions DDPcouldinhibittheactivityofbreastcancer MCF-7 cells.Its mechanisms may be associated with inhibition of MCF-7 cell apoptosis,induction of DNA double strand breaking and the expression of pro-apop-totic protein up-regulating.

关 键 词：MCF-7细胞 顺铂 DNA损伤 乳腺癌 增殖 凋亡 IC(50) 

分 类 号：R329.25[医药卫生—人体解剖和组织胚胎学] R342.3[医药卫生—基础医学]