拉帕替尼诱导Her-2高表达乳腺癌细胞凋亡的机制探讨

摘要

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. Cells 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 MTT assay was used to detected the SKBR-3 cells survival rate, the flow cy-tometry was used to detect the cell apoptosis ,and Western blot assay was used to detectd the expression of P-AKT and sur-vivin. 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.%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500 μg/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.