首页|期刊导航|中华医学杂志（英文版）|Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells
中华医学杂志（英文版）2011，Vol.124Issue(14)：2167-2172,6.DOI:10.3760/cma.j.issn.0366-6999.2011.14.016
Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells
Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells
摘要
Abstract
Background Sodium valproate inhibits proliferation in neuroblastoma and glioma cells, and inhibits proliferation and induces apoptosis in hepatoblastoma cells. Information describing the molecular pathways of the antitumor effects of sodium valproate is limited; therefore, we explored the mechanisms of action of sodium valproate in the human hepatoblastoma cell line, HepG2.Methods The effects of sodium valproate on the proliferation of HepG2 cells were evaluated by the Walsh-sohema transform and colony formation assays. Sodium valproate-induced apoptosis in HepG2 cells was investigated with fluorescence microscopy to detect morphological changes; by flow cytometry to calculate DNA ploidy and apoptotic cell percentages; with Western blotting analyses to determine c-Jun N-terminal kinases (JNK), p-JNK, Bcl-2, Bax, and caspase-3 and-9 protein expression levels; and using JC-1 fluorescence microscopy to detect the membrane potential of mitochondria. Statistical analyses were performed using one-way analysis of variance by SPSS 13.0 software.Results Our results indicated that sodium valproate treatment inhibited the proliferation of HepG2 cells in a dose-dependent manner. Sodium valproate induced apoptosis in HepG2 cells as it: caused morphologic changes associated with apoptosis, including condensed and fragmented chromatin; increased the percentage of hypodiploid cells in a dose-dependent manner; increased the percentage of annexin Ⅴ-positive/propidium iodide-negative cells from 9.52％ to 74.87％; decreased JNK and increased phosphate-JNK protein expression levels; reduced the membrane potential of mitochondria; decreased the ratio of Bcl-2/Bax; and activated caspases-3 and-9.Conclusion Sodium valproate inhibited the proliferation of HepG2 cells, triggered mitochondria-dependent HepG2 cell apoptosis and activated JNK.关键词
hepatoblastoma/sodium valproate/c-Jun N-terminal kinases/mitochondria/apoptosisKey words
hepatoblastoma/sodium valproate/c-Jun N-terminal kinases/mitochondria/apoptosis引用本文复制引用
WANG Wei,LIAO Xiao-li,CHEN Jing-hong,LI Dan-dan,LIN Chun-lan,YAN Yu-xia,TANG Yu-hui,JIANG Jian-wei..Sodium valproate induces mitochondria-dependent apoptosis in human hepatoblastoma cells[J].中华医学杂志（英文版）,2011,124(14):2167-2172,6.基金项目
This study was supported by grants from Sci-Tech Project Foundation of Guangdong Province,China (No.2009B080701051) and the National Natural Science Foundation of China (No.30973811). （No.2009B080701051）
