拉帕替尼诱导Her-2高表达乳腺癌细胞凋亡的机制探讨  

Mechanism of Her-2 overexpressed breast cancer cell apoptosis induced by lapatinib

作　　者：张红[1] 毛晓韵[2] 林哲洙[1] 房月[3] 金锋[2] 

机构地区：[1]辽宁医学院附属第三医院,辽宁锦州110001 [2]中国医科大学附属第一医院 [3]中国医科大学药学院

出　　处：《山东医药》2011年第50期1-3,共3页Shandong Medical Journal

基　　金：国家自然科学基金资助项目(30950009);辽宁省科技厅博士科研启动基金项目(20091110)

摘　　要：目的探讨拉帕替尼诱导Her-2高表达乳腺癌细胞株SKBR-3凋亡的机制。方法取处于对数生长期的SKBR-3细胞,接种于96孔板。随机分为实验组和对照组,每组设6个复孔。实验组加入终浓度500μg/L拉帕替尼,对照组加入含DMSO无血清的DMEM培养液。培养24、48、72 h后,采用MTT法检SKBR-3生存率,用流式细胞仪检测两组细胞凋亡情况,Western blot法检测磷酸化蛋白激酶B(p-AKT)及survivin蛋白。结果拉帕替尼作用24、48、72 h时SKBR-3生存率分别为100%、69.4%、62.0%(P均<0.05)。实验组细胞凋亡率为10.48%,明显高于对照组的2.14%(P<0.05);实验组p-AKT与survivin蛋白相对表达量为0.49±0.12、0.51±0.38,明显低于对照组的1.46±0.13、0.89±0.36(P均<0.05)。结论拉帕替尼诱导Her-2高表达乳腺癌SKBR-3细胞凋亡的机制与其下调p-AKT、survivin蛋白表达有关。Objective To investigate the mechanism of breast cancer SKBR-3 cells apoptosis induced by lapatinib. Methods SKBR-3 cells in log phase were cultured with 96 well plate,and divided to experiment group and control group randomly, 6 wells each. Ceils in experiment group was treated with 500 μg/L lapatinib and the control group was treated with DMSO and DMEM for 24,48,72 h. The MTF assay was used to detected the SKBR-3 cells survival rate, the flow cytometry was used to detect the cell apoptosis , and Western blot assay was used to detectd the expression of P-AKT and survivin. Results The survival rate of SKBR-3 cells cultured with lapatinib for 24,48,72 h were 100% ,69.4% ,62.0% （P 〈0.05）. Compared with control group, the apoptotic rate in experiment group and control group were 10.48% and 2.14% （P 〈0. 05 ）. The relative expression level of P-AKT and survivin were 0.49 ±0.12 and 0. 51±0.38 , but 1.46 ±0. 13 and 0. 89 ±0. 36 in control group （ P 〈 0.05）. Conclusion p-AKT and survivin play important roles in the apoptosis of SKBR-3 cells induced by lapatinib.

关 键 词：人表皮生长因子受体2 乳腺癌 拉帕替尼 细胞凋亡 磷酸化蛋白激酶B 生存素 

分 类 号：R737.9[医药卫生—肿瘤]