阻断PLC-γ1通路对TNF-α抑制胶质瘤细胞增殖并诱导其凋亡的影响  

Sensitization of human glioma SWO cell line to tumor necrosis factor-induced apoptosis by blocking phospholipase C-γ1 signaling pathway

作　　者：林骏[1] 杨进城[1] 谭丽[1] 罗深秋[1] 

机构地区：[1]南方医科大学细胞生物学教研室,广东广州510515

出　　处：《南方医科大学学报》2006年第3期266-269,共4页Journal of Southern Medical University

基　　金：国家自然科学基金项目(39870381);广东省自然科学基金项目(020015);广东省自然科学基金重点项目(05102580)~~

摘　　要：目的探讨磷脂酶C-γ1(PLC-γ1)在肿瘤坏死因子-α(TNF-α)诱导胶质瘤细胞凋亡中的作用。方法应用PLC-γ1的特异性抑制剂U73122抑制SWO胶质瘤细胞PLC-γ1活性,用MTT法观察在阻断PLC-γ1通路前后,TNF-α对SWO胶质瘤细胞的增殖抑制作用;流式细胞仪检测TNF-α诱导SWO胶质瘤细胞凋亡的情况;Western免疫印记法检测TNF-α是否激活caspase-3以及抑凋亡蛋白bcl-2表达的情况。结果抑制PLC-γ1活性后,SWO胶质瘤细胞对低浓度TNF-α的敏感性显著增加。结论阻断PLC-γ1通路本身虽不能直接启动凋亡,但却能增加SWO胶质瘤细胞对某些调亡因素(如TNF-α)的敏感性,其分子机制之一可能是下调抑凋亡基因bcl-2的表达。Objective To explore the role ofphospholipase C-γ1（PLC-γ1） in tumor necrosis factor-α （TNF-α）-induced apoptosis of human glioma SWO cells. Methods The PLC-γ1pathway was blocked by U73122 in SWO cells, and the inhibitory effect of TNF-α on SWO glioma cell proliferation with or without U73122 treatment was investigated by MTT assay. The cell apoptosis induced by TNF-α along or in combination with U73122 was detected by flow cytometry with PI staining. The expression of caspase-3 and Bcl-2 was detected by Western blotting. Results and Conclusion U73122 can sensitize SWO glioma cells to TNF-α-induced apoptosis. Blocking the PLC-γ1 pathway may not induce apoptosis of SWO glioma cells, but can sensitize SWO glioma cells to small-dose TNF-α-induced apoptosis, the mechanism of which may involve down-regulation of bcl-2.

关 键 词：磷脂酶C-γ1胶质瘤 肿瘤坏死因子 细胞凋亡 

分 类 号：R730.2[医药卫生—肿瘤]