蛋白酶体抑制剂通过内质网应激影响前列腺癌DU145细胞的生长  

Proteasome inhibitor affected the growth of prostate cancer cells DU145 via endoplasmic reticulum stress

作　　者：王利平[1] 符鹏程[1] 秦玲[1] 

机构地区：[1]郴州市第一人民医院肿瘤科,湖南郴州423000

出　　处：《现代肿瘤医学》2016年第18期2857-2862,共6页Journal of Modern Oncology

基　　金：郴州市第一人民医院青年基金(编号:N2013-009)

摘　　要：目的:探讨蛋白酶体抑制剂(epoxomicin,EPO)可否诱导前列腺癌DU145细胞产生内质网应激以及内质网应激阻断剂是否可阻断这种作用。方法:不同浓度EPO处理DU145不同时间,MTS检测细胞生长情况,流式细胞仪检测细胞凋亡情况,Real-time PCR检测内质网应激相关分子mRNA表达情况;以及内质网应激阻断剂4-PBA阻断内质网应激后的情况。结果:EPO抑制DU145细胞生长,并呈现浓度梯度依赖;EPO处理组细胞凋亡率明显高于正常组,且EPO 20nmol组凋亡率高于10nmol组;CHOP、XBP-1s、GRP78 mRNA明显升高,72h最为明显;XBP-1及XBP-1s基因转录水平在EPO处理后都升高,而XBP-1s随着处理时间逐渐增加,XBP-1随着时间基因转录水平变化不明显;4-PBA可阻断CHOP mRNA表达,阻断EPO对DU145细胞数量的减少。结论:EPO抑制DU145细胞生长,并促进凋亡,其机制可能与激活内质网应激并激发CHOP、XBP-1s、XBP-1、GRP78分子表达等有关;4-PBA可阻断EPO对细胞生长抑制的影响。Objective： To elucidate the role of EPO in DU145 cells,and the effect of EPO on ER- stress and its association with endoplasmic reticulum stress blocker. Methods： Cell proliferation was detected using MTS reagent and apoptosis was examined by flow cytometer after DU145 cells treated by EPO. Several mRNA associated to ER-stress were tested by real- time PCR and the 4- PBA were used to block the ER- stress. Results： Cell proliferation was inhibited in a time and dose- dependent manner by EPO. The percentage of cell apoptosis on treatment groups was higher than control group and the high- dose group was higher than that of low- dose group. EPO induced ER-stress in DU145 cells time- and dose- dependently induced GRP78,CHOP and XBP- 1s mRNA,and CHOP protein expression. XBP- 1s mRNA expression was raised more obviously than XBP- 1 mRNA with time. CHOP mRNA expression and cell proliferation were blocked by the 4- PBA. Conclusion： The proteasome inhibitor EPO could inhibit cell growth and induce apoptosis on DU145 cells via ER- stress,which may be related to activate the expressions of ER- associated molecules such as CHOP,XBP- 1s,XBP- 1 and GRP78. 4- PBA can block the effect of EPO on cell growth totally.

关 键 词：EPO CHOP GRP78 XBP-1s 内质网应激 4-PBA 

分 类 号：R737.25[医药卫生—肿瘤]