小白菊内酯对U-87 MG细胞增殖和凋亡的影响及其机制研究  

Effects of parthenolide on proliferation and apoptosis of U-87 MG Cells and its mechanism

作　　者：郑捷敏[1] 刘全[1] 陈宏谋[1] 闫宪磊[1] 黎耀[1] 陈家康[1] 

机构地区：[1]广西医科大学第四附属医院,广西柳州545005

出　　处：《现代药物与临床》2015年第5期497-502,共6页Drugs & Clinic

基　　金：广西壮族自治区卫生厅自筹经费科研课题(Z2013624)

摘　　要：目的考察小白菊内酯对于人脑恶性胶质瘤细胞U-87 MG细胞系的增殖、细胞周期及凋亡的影响,并探讨其作用机制。方法采用CCK-8比色法和克隆形成检测法检测小白菊内酯对U-87 MG的增殖抑制作用;采用碘化丙啶(PI)染色后的流式细胞仪检测小白菊内酯处理前后对细胞周期、凋亡的影响;采用q PCR以及Western blotting法研究药物处理后U-87MG细胞的Caspase 3、Bax、Cyclin D1的表达变化以及P53-Ser392蛋白质磷酸化激活。结果小白菊内酯可明显抑制U-87 MG的细胞增殖、克隆形成数量及克隆大小。处理48 h后,U-87 MG细胞的S期、G2/M期受到了阻滞,G0/G1期细胞比例明显减少,同时细胞的凋亡也明显增多。Caspase 3、Bax基因的m RNA及蛋白表达明显上升,而Cyclin D1基因的m RNA表达明显下降。同时P53-Ser392残基的磷酸化水平也明显上升。结论小白菊内酯可通过调节P53基因的Ser392残基磷酸化抑制其下游的细胞凋亡、细胞周期途径上Caspase 3、Bax、Cyclin D1的基因表达,影响细胞周期及凋亡,从而抑制肿瘤细胞的增殖。Objective To study the effects of parthenolide on human malignant glioma cells U-87 MG cell growth, cell cycle regulation, and apoptosis, and explore its mechanism. Methods The inhibition of proliferation on U-87 MG cell ofparthenolide were determined using CCK8 and colony formation assay. Effects on cell cycle and apoptosis changes treated by parthenolide were detected by flow cytometer analysis after PI staining. The expressions of cell cycle and apoptosis related proteins, Caspase 3, Bax, Cyclin D1, and P53-Ser392 were analyzed by qPCR and western blotting. Results Parthenolide significantly inhibited cell proliferation, and induced decrease in the colony formation ability inU-87 MG cells. Treated by parthenolide after 48 h, U-87 MG cell were arrested at S and G2/M phases, the cells proportion at G0/G1 phase decreased, and the apoptotic cells increased. Furthermore, parthenolide could increase the mRNA expression of caspase 3, Bax, and P53-Ser392, while decrease the mRNA expression of Cyclin D1. Conclusion Parthenolide can regulate the Ser392 residue phosphorylation of P53 gene, inhibit apoptosis of downstream cells, and expression of caspase 3, Bax, and Cyclin D1 genes, which effects cell cycle and apoptosis, and induce cellular senescence and apoptosis.

关 键 词：小白菊内酯 人脑恶性胶质瘤细胞U-87 MG P53 凋亡 

分 类 号：R285.5[医药卫生—中药学]