[Coadministration of sorafenib and cisplatin inhibits proliferation of hepatocellular carcinoma HepG2 cells in vitro].
OBJECTIVE
To investigate the inhibitory effect of sorafenib in combination with cisplatin (DDP) on the proliferation of hepatocellular carcinoma cells and explore the molecular mechanisms.


METHODS
The inhibitory effect of sorafenib and DDP treatment on HepG2 cell proliferation in vitro was assessed by MTT assay. The cell cycle changes and the apoptotic rate of the treated cells were detected by flow cytometry, and the expressions of ERK and pERK examined using Western blotting.


RESULTS
Sorafenib and DDP alone both significantly inhibited the proliferation of HepG2 cells, showing a synergistic effect of their actions in combined use (P<0.05). Sorafenib and DDP alone caused cell cycle arrest at G(1) and G(2) phases, respectively. Combined use of the two drugs resulted in significant reduction of the S-phase cell percentage and cell cycle arrest at G(1) and G(2) phases. The coadministration of the drugs significantly increased the apoptosis rate of the cells as compared with the that of the cells with sorafenib or DDP treatment alone (P<0.05). Sorafenib and DDP, used alone or in combination, did not produce obvious effect on ERK expression. Sorafenib treatment for 24 h reduced pERK expression in the HepG2 cells, and the effect was enhanced by combined treatment with sorafenib and DDP.


CONCLUSIONS
Sorafenib and DDP show a synergistic effect in inhibiting the proliferation and inducing apoptosis of HepG2 cells. The mechanisms of this synergistic effect can be closely related to the double blockage of the cell cycle and Raf/MEK/ERK pathway inhibition.
Chen
Feng-sheng
FS
Oncology Center, Nanfang Hospital, Southern Medical Unversity, Guangzhou, China. fsc0126@163.com
Cui
Yan-zhi
YZ
Luo
Rong-cheng
RC
Wu
Jing
J
Zhang
Hua
H
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D001557:Benzenesulfonates / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002945:Cisplatin / Q000494:pharmacology*; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D002945:Cisplatin