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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 inhibitory effect of Smac small molecule compound 3 on cisplatin on the apoptosis and growth of ovarian cancer cell line SKOV3. Methods The growth inhibition rate and survival rate of ovarian cancer cell line SKOV3 were detected by the method of thiazolyl blue (MTT) assay, and the growth curve was established by using the combination of Smac small molecule compound 3 alone, cisplatin alone and the combination of the two. Annexin V / PI double-labeled flow cytometry was used to detect the effect of Smac small molecule compound 3 alone, cisplatin alone, and a combination of both on SKOV3 apoptosis. Western blotting was used to detect the expression of X-linked inhibitor of apoptosis protein (XIAP) and cysteine-aspartate (SKOV3) in SKOV3 cells treated with compound 3 of Smac alone, cisplatin alone, Effect of caspase-3 expression. Results The growth of SKOV3 was inhibited in a time-dependent manner in Smac small molecule compound 3 alone group, cisplatin alone group and the combination of the two groups at 12, 24 and 48 h. The combination of the two groups and cisplatin alone application group growth inhibition rate was significantly higher. The apoptosis rate of the two combination groups was higher than that of cisplatin alone group and Smac small molecule compound 3 alone group. Smac small molecule compound 3 alone and combination of the two groups decreased the expression of SKAP3 XIAP, the combined application of caspase-3 activation fragment was significantly higher than the other two groups. Conclusion Smac small molecule 3 can modulate the inhibitory effect of cisplatin on the growth of SKOV3 cells and promote the apoptosis of ovarian cancer cell line SKOV3. The Smac small molecule compound 3 achieves its pro-apoptotic and growth-inhibitory effects by affecting the expression of XIAP.