[Inhibitory effect of sorafenib combined with arsenic trioxide on hepatocellular carcinoma cells].
OBJECTIVE
To investigate the inhibitory effect of sorafenib in combination with arsenic trioxide (As2O3) on hepatocellular carcinoma cells and explore the mechanisms of the synergetic antitumor effects of the two agents.


METHODS
HepG2 cells were treated with sorafenibor, As2O3 alone or their combination, with the untreated cells used as the control. The inhibitory effect of the treatment was analyzed by MTT assay, and the cell apoptosis and mitochondrial transmembrane potential (delta phi m) were detected by flow cytometry. Western blotting was performed to examine the expressions of ERK and pERK in the cells.


RESULTS
Sorafenib and As2O3 used alone or in combination both inhibited the proliferation of HepG2 cells, and a synergistic effect of the two agents was noted in their combined action (P<0.05). Combined treatment of the cells resulted in significantly higher apoptsis rate than that in the other groups (P<0.05), and was associated with a more obvious decrease in delta phi m. The expression of ERK was not affected by the two agents used either alone or in combination, but pERK expression was significantly lowered in the cells after combined treatment for 24 h.


CONCLUSIONS
A synergistic effect is observed between the sorafenib and As2O3 in their inhibition of HepG2 cell proliferation, the mechanisms of which may involve reduction of mitochondrial transmembrane potential and Raf/MEK/ERK pathway inhibition.
Wu
Jing
J
Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515ì China. wujing81@fimmu.com
Luo
Rong-cheng
RC
Zhang
Hua
H
Cui
Yan-zhi
YZ
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D001557:Benzenesulfonates / Q000494:pharmacology*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009536:Niacinamide / Q000031:analogs & derivatives; D010087:Oxides / Q000494:pharmacology*; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib
D000970:Antineoplastic Agents; D001152:Arsenicals; D001557:Benzenesulfonates; D010087:Oxides; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib; D048049:Extracellular Signal-Regulated MAP Kinases; D000077237:Arsenic Trioxide