mda-7/IL-24 induces apoptosis of hepatic carcinoma cells through endoplasmic reticulum stress pathway
10.3724/SP.J.1008.2008.01020
- Author:
Xiao-Feng ZHANG
1
Author Information
1. Department of Comprehensive Treatment
- Publication Type:Journal Article
- Keywords:
Apoptosis;
Endoplasmic reticulum;
Liver neoplasms;
mda-7 gene;
Stress
- From:
Academic Journal of Second Military Medical University
2010;29(9):1020-1024
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To study the effects of mda-7/IL-24 on the growth, proliferation, apoptosis of different hepatic carcinoma cell lines and the related mechanisms. Methods: A recombinant adenovirus Ad-mda-7 was constructed and was used to transfect human hepatic carcinoma cell lines (HepG2, Hep3B and PLC/ PRF/5) and normal liver cell line L02. MTT assay and FACS were employed to assess the growth and apoptosis of cells; the expression of related protein expression was examined by Western blotting. The cells were treated with calpastatin I (ALLN,25 μmol/L) for 30 min to block the endoplasmic reticulum stress (ER-stress) and the above indices were examined again. Results: Treatment with Ad-mda-7 resulted in selective inhibition of cell proliferation and induced apoptosis, especially in HepG2 cells; Ad-mda-7 showed no influence on normal cells. Pretreatment with ALLN partially inhibited the above effects of Ad-mda-7. Western blotting revealed that Ad-mda-7 induced up-regulation of BiP/GRP7B and Bax protein, activation of caspase-12, caspase-3 and phosphorylation of p38 MAPK in HepG2 cells. Blocking ER-stress with ALLN down-regulated Bax, caspase-12 expression and inhibited activation of caspase-3 and caspase-12, but showed no effect on the expression of BiP/GRP78 or phosphorylation of p38 MAPK. Conclusion: mda-7/IL-24 can cause growth inhibition and promote apoptosis of hepatic carcinoma cells through the ER-stress pathway.
