Smac小分子compound3调节顺铂诱导卵巢癌细胞SKOV3凋亡的研究  

Smac mimic potentiates cisplatin-induced cell apoptosis of ovarian cancer cells

作　　者：乔真[1] 刘培淑[2] 韩冰[1] 王毓[1] 

机构地区：[1]山东大学医学院,济南250012 [2]山东大学齐鲁医院妇产科,济南250012

出　　处：《山东大学学报（医学版）》2012年第6期61-64,69,共5页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金面上项目(30872739)

摘　　要：目的探讨Smac小分子compound 3调节顺铂对卵巢癌细胞SKOV3凋亡及生长抑制作用。方法噻唑蓝法检测Smac小分子compound 3单独应用组、顺铂单独应用组及二者联合应用组对卵巢癌细胞SKOV3的生长抑制率、存活率的影响;并绘制生长曲线。Annexin V/PI双标流式细胞术检测Smac小分子compound 3单独应用组、顺铂单独应用组及二者联合应用组对SKOV3凋亡率的影响。Western印迹检测Smac小分子compound 3单独应用组、顺铂单独应用组及二者联合应用组对SKOV3的X连锁凋亡抑制蛋白(X-linked inhibitor of apoptosisprotein,XIAP)、半胱氨酸-天冬氨酸蛋白酶-3(caspase-3)的表达影响。结果 Smac小分子compound 3单独应用组、顺铂单独应用组及二者联合应用组12、24、48 h SKOV3生长受到抑制,且呈时间依赖性。二者联合应用组与顺铂单独应用组比较生长抑制率明显升高。二者联合应用组的凋亡率高于顺铂单独应用组及Smac小分子compound 3单独应用组。Smac小分子compound 3单独应用组及二者联合应用组SKOV3的XIAP表达降低,二者联合应用组的caspase-3的激活片段表达明显高于其他两组。结论 Smac小分子compound 3能够调节顺铂对SKOV3生长抑制作用,促进顺铂对卵巢癌细胞SKOV3凋亡作用。Smac小分子compound 3通过影响XIAP的表达来实现其促凋亡及生长抑制作用。Objective To investigate the effect of a small Smac mimic molecule （ compound 3 ） on cisplatin-induced cell apoptosis and growth inhibition of ovarian cancer cell lines. Methods Cell viability and the growth inhibition ratio of the ovarian cancer cell lines SKOV3 were measured by MTT in the compound 3-treated group, the cisplatin-treated group and the combination treatment group. Apoptosis and protein expression were detected by flow cytometry and Western blot. Results Cell viability was inhibited in the three groups, and it was time-dependent. The growth inhibi- tion ratio of SKOV3 in the combination treatment group was more significantly increased than the cisplatin-treated group, and the apoptotic rate of SKOV3 in the combination treatment group was more significantly increased than in the other groups. Expressions of XIAP in SKOV3 ceils were decreased in the compound 3-treated group and the combina- tion treatment group. Activated fragments of caspase 3 in the combination treatment group were more increased than in the other groups. Conclusion Treatment with compound 3 enhances growth inhibition and apoptosis of SKOV3 in- duced by cisplatin. The pro-apoptotic effect of compound 3 was correlated with expression of XIAP.

关 键 词：卵巢肿瘤 Smac小分子compound 3 SKOV3细胞 细胞凋亡 顺铂 

分 类 号：R711.75[医药卫生—妇产科学]