[Coadministration of sorafenib and cisplatin inhibits proliferation of hepatocellular carcinoma HepG2 cells in vitro].

Abstract

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.

• Authors: Feng-sheng Chen, Yan-zhi Cui, Rong-cheng Luo, Jing Wu, Hua Zhang
• Journal: Nan fang yi ke da xue xue bao = Journal of Southern Medical University (Nan Fang Yi Ke Da Xue Xue Bao) Vol. 28 Issue 9 Pg. 1684-7 (Aug 2008) ISSN: 1673-4254 [Print] China
• PMID: 18819900 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzenesulfonates
• Phenylurea Compounds
• Pyridines
• Niacinamide
• Sorafenib
• Extracellular Signal-Regulated MAP Kinases
• Cisplatin

Topics

• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Benzenesulfonates (pharmacology)
• Blotting, Western
• Carcinoma, Hepatocellular (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Drug Synergism
• Extracellular Signal-Regulated MAP Kinases (metabolism)
• Flow Cytometry
• Humans
• Liver Neoplasms (metabolism, pathology)
• Niacinamide (analogs & derivatives)
• Phenylurea Compounds
• Pyridines (pharmacology)
• Sorafenib