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冬凌草甲素通过抑制亚甲基四氢叶酸脱氢酶2诱导肝癌细胞凋亡 被引量:1
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作者 黄应文 黄岩屹 +3 位作者 王瑶瑶 刘宏元 朱明阳 刘晓宁 《中医临床研究》 2022年第17期6-9,共4页
目的:探讨亚甲基四氢叶酸脱氢酶2(Methylene Tetrahydrofolate Dehydrogenase 2,MTHFD2)在冬凌草素诱导人肝癌细胞HepG2细胞凋亡中的作用及其机制。方法:通过冬凌草甲素处理HepG2细胞24 h,蛋白质免疫印迹技术检测MTHFD2、Ras基因(Ras)... 目的:探讨亚甲基四氢叶酸脱氢酶2(Methylene Tetrahydrofolate Dehydrogenase 2,MTHFD2)在冬凌草素诱导人肝癌细胞HepG2细胞凋亡中的作用及其机制。方法:通过冬凌草甲素处理HepG2细胞24 h,蛋白质免疫印迹技术检测MTHFD2、Ras基因(Ras)、磷酸激酶B(Akt)、磷酸化蛋白激酶B(p-Akt)、胞外调节蛋白激酶(ERK)、胞外调节蛋白激酶磷酸化(p-ERK)和C-Myc癌基因(c-Myc)蛋白的表达;以酶联免疫吸附剂测定(Enzyme-linked Immunosorbent Assay,ELISA)试剂盒检测MTHFD2的酶活性;采用Annexin V-FITC/碘化丙啶凋亡检测试剂盒检测凋亡比例;Giemsa染色观察细胞克隆;通过分子对接研究MTHFD2与冬凌草甲素可能的结合模型。结果:冬凌草甲素对MTHFD2的抑制呈剂量依赖性;MTHFD2的抑制引起线粒体活性氧物质(Reactive Oxygen Species,ROS)升高,表现为线粒体ROS清除剂N-乙酰-L-半胱氨酸(N-Acetyl-L-Cysteine,NAC)的处理使细胞克隆形成和细胞凋亡比例逆转;冬凌草甲素通过Ras、p-Akt和c-Myc抑制MTHFD2。结论:冬凌草甲素通过Ras-Akt-Myc信号通路抑制MTHFD2,介导线粒体ROS升高,从而导致HepG2细胞凋亡。 展开更多
关键词 亚甲基四氢叶酸脱氢酶2 冬凌草甲素 线粒体活性氧物质 肝癌 HEPG2细胞
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Effects of dichloroacetate on the activation of the mitochondrial pathway in C6 cells in vitro
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作者 赵欣 王欣 +5 位作者 余克富 段瑀 李捷思 赵炳祥 张烜 张强 《Journal of Chinese Pharmaceutical Sciences》 CAS 2011年第5期460-465,共6页
Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochond... Mitochondria are increasingly recognized as important targets for tumor treatment because of their central roles in apoptotic pathways and cellular metabolism. Dichloroacetate (DCA), a low molecular weight mitochondria-targeting agent, exhibits potential therapeutic effects for tumors. Based on the effects of DCA on tumor cellular metabolism, we carried out this study to investigate the anti-tumor activity of DCA in C6 glioma cells in vitro. The results showed that DCA was able to increase the activity of pyruvate dehydrogenase (PDH), induce the production of reactive oxygen species (ROS) and reduce the mitochondrial membrane potential (MMP) in C6 ceils in vitro (P〈0.05 or 0.01), indicating that the anti-tumor effects of DCA in C6 cells could be through the activation of the mitochondrial pathway. In conclusion, mitochondria could be a viable therapeutic target for the treatment of glioma. 展开更多
关键词 Mitochondria metabolism DICHLOROACETATE C6 glioma Pyruvate dehydrogenase Reactive oxygen species Mitochondrial membrane potential
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