摘要
目的探讨二氯乙酸(DCA)增强替莫唑胺(TMZ)对人脑胶质瘤细胞的抑制作用及机制。方法通过体外实验,观察DCA单药、TMZ单药以及DCA/TMZ联合对人脑胶质瘤细胞的抑制作用;MTT比色法检测细胞增殖;流式细胞技术检测细胞凋亡及细胞内活性氧(ROS)的变化;激光共聚焦显微镜检测细胞线粒体膜电位(MMP);蛋白质印迹法检测细胞低氧诱导因子(HIF-1α)和p53凋亡通路相关蛋白的表达。结果 DCA/TMZ联合更有效抑制胶质瘤细胞增殖、使MMP降低、细胞内ROS增加、细胞凋亡增加;HIF-1α表达下降、p53表达升高。结论 DCA能增强TMZ对人脑胶质瘤细胞的抑制作用,其机制与抑制HIF-1α、激活p53凋亡信号通路有关。
Objective To investigate the antitumor effect of dichloroacetate （DCA） combined with temozolomide （TMZ） on human glioma in vitro and to explore the mechanism. Methods In vitro experiments, the inhibitory effects of DCA alone, TMZ alone and DCA/TMZ combination on SHG44 cells were determined by MTT assay. Cell viability was measured by MTT assay; apoptotic cells and intracellular ROS were detected by flow cytometry. The alteration of mitochondrial membrane potential （MMP） was determined by confocal laser scanning microscopy. Western blot was used to detect the expressions of HIF-1α and p53 pathway-related protein in tumOr tissues. Results DCA depolarized mitochondria, increased mitochondrial ROS, and induced apoptosis in human glioma cells in vitro, thus inhibiting cell growth significantly. The inhibition rate of DCA/TMZ combination groups on SHG44 cells growth was significantly higher than that of DCA or TMZ alone. TMZ and DCA decreased the expression levels of HIF-1αand promoted p53 activation in vitro. Oonclusion DCA combined with TMZ inhibits human glioma cells through inhibiting HIF-1α and promoting p53 apoptosis signaling pathway.
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2014年第1期51-55,68,共6页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
陕西省卫生厅基金资助项目(No.2012D20)~~
关键词
胶质瘤
缺氧诱导因子1A
有氧糖酵解
线粒体功能障碍
P53
替莫唑胺
二氯乙酸
glioma
hypoxia-inducible factor-lalpha （HIF-1α）
aerobic glycolysis
mitochondrial disfunction
p53
temozolomide （TMZ）
dichloroacetate （DCA）
