Mda-7-carrying replication-defective adenovirus selectively kills hepatocellular carcinoma cells by facilitating release of proapoptotic protein from mitochondria.
- Author:
Cong-Jun WANG
1
;
Zhi-Hai PENG
;
Jian-Wei ZHENG
;
Kun CHEN
;
Hui-Yi HU
;
Wen-Wei JI
;
Yuan YU
;
Xin-Bo XUE
Author Information
- Publication Type:Journal Article
- MeSH: Adenoviridae; genetics; Apoptosis; Caspase 9; metabolism; Cytochromes c; metabolism; Hep G2 Cells; Hepatocytes; cytology; Humans; Interleukins; genetics; metabolism; Intracellular Signaling Peptides and Proteins; metabolism; Mitochondria; metabolism; Mitochondrial Proteins; metabolism; Proto-Oncogene Proteins c-bcl-2; metabolism; Transfection; bcl-2-Associated X Protein; metabolism; bcl-X Protein; metabolism
- From: Chinese Journal of Oncology 2008;30(9):649-653
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the mechanism that mda-7/IL-24 selectively kills hepatocellular carcinoma (HCC) HepG2 cells in vitro.
METHODSHCC cell line HepG2 and normal liver cell line L02 were infected with Ad.mda-7. The expression of mda-7/IL-24 was detected by RT-PCR and ELISA, respectively. The apoptotic effects were confirmed by Hoechst staining and flow cytometry assay, respectively. Furthermore, Bcl-2 family proteins, cytochrome C, Smac/DIABLO and caspase-9 were determined by Western blot.
RESULTSThe exogenous mda-7/IL-24 gene was expressed in HepG2 and L02 cells infected with Ad.mda-7. Ad.mda-7 induced apoptosis in HepG2 but not in L02 cells in vitro. The induction of tumor cell apoptosis is correlated with the increasing expression of Bax and decreasing expression of Bcl-2 and Bcl-xL genes, then facilitated the releasing of cytochrome C and Smac/DIABLO from mitochondria to cytoplasm and increasing the expression of caspase-9, eventually, resulted in apoptosis.
CONCLUSIONAd.mda-7 selectively induces growth inhibition and apoptosis in hepatocellular carcinoma HepG2 cells but not in normal L02 hepatocytes in vitro, and the mechanism might involve the decrease of Bcl-2 and Bcl-xL and increase of Bak expression, facilitating the release of cytochrome C and Smac/DIABLO from mitochondria in HCC cells.
