Tyrphostins AG1478对内分泌耐药乳腺癌细胞的作用  

The effect of tyrphostins AG1478 to anti-endocrine breast cancer cells

作　　者：甄林林[1] 朱旬[1] 郑伟[1] 王萱仪[1] 武正炎[1] 

机构地区：[1]南京医科大学第一附属医院乳腺外科,江苏南京210029

出　　处：《南京医科大学学报（自然科学版）》2006年第7期530-533,共4页Journal of Nanjing Medical University(Natural Sciences)

摘　　要：目的:研究表皮生长因子受体(EGFR)抑制剂对内分泌治疗耐药的激素依赖性乳腺癌细胞的作用,探讨EGFR抑制剂的应用前景。方法:选择雌激素受体(ER)阳性的乳腺癌细胞MCF-7,建立三苯氧胺(TAM)耐药的乳腺癌细胞(T-MCF-7)。研究EGFR抑制剂TyrphostinsAG1478对T-MCF-7细胞的作用,采用四甲基偶氮唑蓝(MTT)比色法进行细胞生长抑制试验,流式细胞仪(FCM)检测细胞周期的影响,Westernblot方法分析EGFR及其信号通路的改变。结果:MCF-7细胞在持续给予TAM(10-7mol/L)处理6个月后获得耐药细胞T-MCF-7。与MCF-7细胞相比,T-MCF-7对AG1478的敏感性增高。AG1478可使T-MCF-7细胞周期阻滞,增殖指数下降,凋亡率增加;对T-MCF-7细胞的EGFR和细胞外信号调节激酶(ERK1/2)蛋白水平无影响,但使其磷酸化-ERK1/2水平下降,降低了EGFR下游信号通路的活性水平。结论:激素依赖性乳腺癌细胞给予TAM长期处理后,更依赖于EGFR信号转导通路的作用。EGFR抑制剂可抑制EGFR信号通路的活性,提高乳腺癌内分泌治疗的效果。Objective： To investigate the function of epidermal growth factor receptor （EGFR） inhibitor to anti-endocrine estrogendepend breast cancer cells, and the clinical prospects of EGFR inhibitors. Methods： Anti-endocrine breast cancer cells （T-MCF-7） was established by estrogen receptor positive （ER＋） breast cancer cells（MCF-7） keeping on exposing to Tamoxifen （TAM） for an enough time. The effect of Tyrphostins AG1478 to T-MCF-7 cells was studied including the cell growth inhibitory test by MTT method, the cell cycles by flow cytometry （FCM）, the proteins expression of EGFR,extracellular signal-regulated kinase （ERK1/2） and phosphorylation-ERKl/2 by western blot,respectively. Results： MCF-7 cells have been becoming anti-endocrine cells（T-MCF-7） after exposing to TAM for about six months. Comparing to MCF-7, T-MCF-7 was more sensitive to the EGFR inhibitor Tyrphostins AG1478. After being exposed to Tyrphostins AG1478, the T-MCF-7 cells was discovered the cell cycles was blocked, the apoptosis rate increased, the proliferation index （PI） and the express of p-ERK1/2 protein decreased, while the express of EGFR and ERK1/2 protein has no changes. Conclusions： T-MCF-7 cells,estrogen-depend breast cancer cells exposing to TAM for a long time, would depend on the fimction of EGFR signaling transduction pathway. EGFR inhibitors would depress the activity of EGFR down-signaling pathway and increase the endocrine therapeutic effects of the breast cancer.

关 键 词：乳腺癌 内分泌治疗 表皮生长因子受体 抑制剂 

分 类 号：R737.9[医药卫生—肿瘤]