摘要
背景与目的:蛋白激酶C(protein kinase C,PKC)参与肿瘤的发生、发展及预后。本研究探讨蛋白激酶Cα(Protein kinase Cα,PKCα)在人神经胶质瘤耐药细胞株SHG-44/ADM发生细胞凋亡中的作用和机制。方法:应用阿霉素浓度递增和间歇诱导法建立SHG-44/ADM耐药株,采用PKCα激活剂PMA和抑制剂Staurosporine分别干预SHG-44/WT和SHG-44/ADM细胞株,激酶分析PKCα活性,荧光分光光度计检测细胞内阿霉素浓度,流式细胞仪检测细胞凋亡率。结果:PKCα激活剂PMA增强细胞PKCα和MDR-1的活性,同时降低细胞凋亡率;PKCα抑制剂Staurosporine抑制细胞PKCα和MDR-1的活性,增加细胞凋亡率。结论:PKCα通过MDR-1参与神经胶质瘤耐药细胞的凋亡。
BACKGROUND ＆ OBJECTIVES： Protein kinase C is associated with the initiation, progression and treatment-resistance of tumors. In this study, we investigated the molecular mechanism and effect of protein kinase Ca in apoptosis of drug-reslstant human glioma SHG-44/ADM cell line. METHODS： Drug-resistant glioma cell line SHG-44/ADM was established by intermittently treating SHG-44 cells with increasing adriamyein. SHG-44/WT and SHG-44/ADM were treated with adriamyein combined with either PKCα activator PMA or PKCα inhibitor Staurosporine. PKCα activity was determined by kinase assay. Adriamycin accumulation was determined by fluorescence spectrometry, and apoptosis was measured with flow eytometry. RESULT： PMA increased PKCα and MDR-1 activity, and inhibited apoptosis induced by adriamyein. Whereas, staurospofine inhibited PKCα and MDR-1 activity, and enhanced apoptosis induced by adriamyein. CONCLUSIONS： The resistance of human glioma to adriamycin is mediated by PKCα via MDR-1.
出处
《中国神经肿瘤杂志》
2009年第2期82-85,共4页
Chinese Journal of Neuro-Oncology
