拉帕替尼诱导Her－2高表达乳腺癌细胞凋亡的机制探讨

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、72h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、72h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。

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

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.