XIAP抑制剂Embelin体外对人胰腺癌细胞株的抑制效应与机制研究

Inhibitive effect of a XIAP inhibitor Embelin on human pancreatic carcinoma cells and its mechanism

目的探讨XIAP小分子抑制剂Embelin体外对人胰腺癌细胞株MIAPaCa-2的抑制效应与机制。方法将生长至第4-12代之间的MIAPaca-2细胞分为DMSO对照组与Embelin实验组,在实验组细胞中加入不同浓度的Embelin共孵育72h,收集细胞并裂解后取上清液用细胞凋亡试剂盒检测组蛋白(凋亡指标)的OD值水平。MIAPaca-2细胞加入不同浓度的Embelin共孵育60h后再加入3H胸腺嘧啶继续孵育12h,取细胞裂解液用同位素γ闪烁计数仪检测3H-CPM数值以判断细胞增殖程度。对DMSO对照组与Embelin实验组的组蛋白OD值与3H-CPM数值分别进行比较分析。结果Embelin实验组的MIAPaCa-2细胞株组蛋白OD值显著高于DMSO对照组而3H-CPM数值明显低于DMSO对照组(P<0.01),且实验组Embe-lin的作用浓度与组蛋白OD值呈正相关(r=0.996,P<0.01),而与3H-CPM数值呈负相关(r=-0.993,P<0.01)。结论Embelin呈剂量依赖性地诱导人胰腺癌细胞株MIAPaCa-2凋亡并抑制其增殖,有肿瘤抑制效应。

Objective To explore the inhibitive effect of Embelin, a small molecule XIAP inhibitor, on human pancreatic carcinoma cells MIAPaCa-2 and its mechanism. Methods MIAPaCa-2 ceils of generation 4 to generation 12 were divided into Embelin group and DMSO control group. MIAPaCa-2 ceils in Embehn group were cultured with different concentrations of Embehn for 72 h,harvested and lysed. And then histone levels were determined with cell death detection ELISAPLUs kit. MIAPaCa-2 cells were cultured with different concentrations of Embelin for 60 h, and then cultured with 3H thymidine for 12 h. Then 3 H-CPM values were measured with scintillation counter in cell lysis supernatants. Results OD values of histone in Embelin group were higher than those in DMSO control group （P 〈 0.01 ）, while 3 H-CPM values in Embelin group were lower than those in DMSO control group （P 〈 0.01 ）. Embelin concentrations in Embelin group were positively related with histone OD values （ r = 0. 996, P 〈 0.01 ）, but negatively related with 3 H-CPM values （ r = - 0.993, P 〈 0.01 ）. Conclusion Embelin may have anti-tumor effect on human carcinoma cells by inducing the apoptosis of human pancreatic carcinoma cell MIAPaCa-2 and inhibiting dose-dependently its proliferation.