c-Met抑制剂SGX523诱导乳腺癌MDA-MB-231细胞系的凋亡  

c-Met Inhibitor SGX523-induced Apoptosis of Breast Cancer Cells MDA-MB-231

作　　者：冯炜红[1] 张斌[1] 赵洪猛[1] 张月[1] 李媛媛[1] 陈祖锦[1] 刘博文[1] 曹旭晨[1] 

机构地区：[1]天津医科大学附属肿瘤医院乳腺一科乳腺癌防治教育部重点实验室天津市肿瘤防治重点实验室,天津市300060

出　　处：《中国肿瘤临床》2012年第2期61-64,共4页Chinese Journal of Clinical Oncology

基　　金：国家自然科学基金(编号:81001186);天津市自然科学基金(编号:10JCYBJC14100)资助~~

摘　　要：目的:研究c-Met小分子抑制剂SGX523对人乳腺癌细胞株的增殖抑制和凋亡诱导作用。方法:以不同浓度的SGX523作用于乳腺癌细胞MDA-MB-231。采用四甲基偶氮唑蓝(MTT)法检测细胞增殖,流式细胞仪检测细胞周期和细胞凋亡,Western blot法检测凋亡相关蛋白半胱氨酸天冬氨酸蛋白酶(Caspase-3)、PARP的表达和c-Met及Akt磷酸化水平的变化。结果:SGX523能明显抑制乳腺癌细胞的增殖(P<0.05),其对MDA-MB-231细胞的半数抑制浓度(IC_(50))值为(0.767±0.115)μmoL/L。SGX523处理MDA-MB-231细胞48 h后,可诱导乳腺癌细胞凋亡和细胞周期G_0/G_1期阻滞。同时,SGX523可促进凋亡相关蛋白Caspase-3和PARP的剪切,并有效抑制c-Met及AKT的磷酸化水平,呈一定的剂量依赖关系。结论:c-Met抑制剂SGX523通过诱导凋亡和G_0/G_1期阻滞来抑制人乳腺癌MDA-MB-231细胞生长,其机制可能与c-Met/PI3K/AKT信号转导通路的磷酸化水平受抑制相关。Objective： To examine the growth inhibition and apoptosis induction effects of a c-Met-specific small-molecule inhib- itor SGX523 on human breast cancer cells MDA-MB-231. Methods： Breast cancer cell line MDA-MB-231 was treated with different concentrations of SGX523. Cell growth was assessed by MTT assay. Cell cycle alteration and cell apoptosis were examined by flow cy- tometry. Expression of apoptosis-related protein Caspase-3 and PARP were determined by Western blot, which was also used to analyze the phosphorylation levels of c-Met and Akt. Results： SGX523 evidently inhibited the growth of breast cancer cells MDA-MB-231 （ P 〈 0.05 ）, with an ICS0 value of （ 0.767 ~ 0.115 ） gmol/L. The effect displayed an obvious dose-effect relationship. Apoptosis induc- tion and GdGI cell cycle arrest, which were examined by flow cytometry （ P 〈 0.05 ）, were observed in SGX523-treated cells. Com- pared with the control group, SGX523 could dose-dependently promote the dissection of apoptosis-related protein Caspase-3 and PARR Moreover, this molecule inhibited the phosphorylation of c-Met and its downstream key protein Akt. SGX523 had no significant effect on the expression of c-Met and Akt. Conclusion： c-Met inhibitor SGX523 can reduce cell growth and induce apoptosis and G0/G1 cell cycle arrest in breast cancer cell line MDA-MB-231. These effects may be achieved through inhibiting phosphorylation of c-Met/ PI3K/Akt.

关 键 词：乳腺癌 C-MET 凋亡 周期阻滞 

分 类 号：R737.9[医药卫生—肿瘤]