RASSF1A expression inhibits cell growth and enhances cell chemosensitivity to mitomycin in BEL-7402 hepatocellular carcinoma cells.
BACKGROUND
The antitumor role of Ras association domain family 1A (RASSF1A) gene and its potential molecular mechanisms are not well understood. The objective of this study was to observe the antitumor ability of RASSF1A in hepatocellular carcinoma, and study the mechanisms of cell apoptosis induced by RASSF1A.


METHODS
After stably transfecting a RASSF1A (wild-type or mutant) expression vector into the BEL-7402 hepatocellular carcinoma cell line, RT-PCR and Western blotting was used to detect the RASSF1A expression levels in recombinant cells. The effects of wild-type RASSF1A on cell growth were observed in vitro by analyzing cell proliferation rate, cell colony formation, and in vivo by analyzing tumorigenesis in nude mice. In addition, the effect of RASSF1A gene expression on the chemosensitivity of human hepatocellular carcinoma cells to antitumor drugs was examined by inhibition of cell proliferation and the percentage of apoptotic cells.


RESULTS
Wild-type RASSF1A, not the mutant, suppressed cell growth in vitro and in vivo. Re-expression of wild-type RASSF1A could enhance the inhibition of cell proliferation and the percentage of apoptotic cells following cell treatment with mitomycin, but had no significant effect when combined with adriamycin, etoposide, 5-fluorouracil and cisplatin treatment.


CONCLUSIONS
Wild-type RASSF1A inhibits cell growth and enhances cell chemosensitivity to mitomycin in hepatocellular carcinoma, suggesting that RASSF1A may serve as a new target for gene therapy in hepatocellular carcinoma patients.
Guan
Hong-geng
HG
Department of General Surgery, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.
Xue
Wan-jiang
WJ
Qian
Hai-xin
HX
Zhou
Xiao-jun
XJ
Qin
Lei
L
Lan
Jing
J
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D016685:Mitomycin / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D000970:Antineoplastic Agents; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D016685:Mitomycin