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目的:探讨Bcl-2相关抗凋亡基因3(Bcl-2-associated athanogene3,BAG3)在蛋白酶体抑制剂诱导肿瘤细胞凋亡中的作用。方法:选取不同组织来源的人肿瘤细胞系,分别设空白对照组、蛋白酶体抑制剂MG132处理组、衣霉素处理组及特异性siBAG3、随机序列核酸si RNA和错位型siBAG3组;利用实时定量RT-PCR法检测各组细胞BAG3及葡萄糖调节蛋白78(glucose regulated protein78,GRP78)mRNA表达;流式细胞仪(FCM)检测细胞凋亡。结果:与空白对照组相比,MG132能显著增加有关细胞BAG3基因表达水平(P<0.01);而衣霉素处理组细胞BAG3表达变化差异无统计学意义,P>0.05,但明显增加GRP78表达(P<0.01);siBAG3组细胞BAG3表达水平显著低于随机序列核酸si RNA和si mut-BAG3组(P<0.01),siBAG3组细胞凋亡率差异有统计学意义,P<0.01。结论:BAG3是影响蛋白酶体抑制剂凋亡效应的一类破坏因子,下调其表达有望增加蛋白酶体抑制剂抗肿瘤活性。
AIM: To investigate the role of Bcl-2-associated athanogene3 (BAG3) in the apoptosis of tumor cells induced by proteasome inhibitor. Methods: The human tumor cell lines from different tissues were selected and divided into blank control group, MG132 proteasome inhibitor group, tunicamycin group, siBAG3 group, random RNA and siBAG3 group respectively. Real-time quantitative The mRNA expression of BAG3 and GRP78 in each group was detected by RT-PCR. The apoptosis was detected by flow cytometry (FCM). Results: Compared with the blank control group, MG132 significantly increased the expression of BAG3 gene (P <0.01), while there was no significant difference in the expression of BAG3 in tunicamycin group (P> 0.05), but significantly increased the expression of GRP78 (P <0.01). The expression of BAG3 in siBAG3 group was significantly lower than that of siRNA-siRNA-siRNA and si mut-BAG3 group (P <0.01). The apoptosis rate in siBAG3 group was significantly different (P <0.01). CONCLUSION: BAG3 is a kind of disrupting factor that affects the apoptosis effect of proteasome inhibitor. Decreasing its expression may increase the antitumor activity of proteasome inhibitor.