[Sorafenib reverses multidrug resistance of hepatoma cells in vitro].
OBJECTIVE
To explore the role of sorafenib in reversing multidrug resistance (MDR) in hepatoma BEL-7402/FU cells and its possible mechanisms.


METHODS
MTT colorimetric assay was used to obtain the dose-response curve of sorafenib in BEL-7402/FU cells, and flow cytometry performed to assess the effect of sorafenib on Rho123 concentration in the cells. The optimal dose of sorafenib for cell treatment was determined according to the results of MTT assay and flow cytometry. MTT assay was employed to evaluate the effect of sorfenib on the cytotoxicity of the antitumor drugs, flow cytometry performed to determine the expression of cell membrane transport protein (P-gp), and RT-PCR used to detect mdr1 gene expression in the cells treated with sorafenib at the optimal dose.


RESULTS
Sorafenib at the concentration of 4 micromol/L, efficiently reversed the MDR of the cells with minimal side effects. At the concentration of 4 micromol/L, sorafenib partially reversed the drug resistance of BEL-7402/FU cells to ADM, 5-FU, GEM and DDP, with reversal indexes of 2.98, 7.16, 1.99 and 10.08, respectively. Treatment of the cells with 4 micromol/L, sorafenib also partially down-regulated P-gp expression in BEL-7402/FU cells, and caused a reduction of mdr1 gene expression by 27.3% in comparison with the control cells.


CONCLUSIONS
Sorafenib can reverse MDR in human hepatoma cells probably in association with down-regulation of mdr1 gene expression and increased accumulation of the chemotherapeutic agents in the cells.
Wei
Li
L
Center of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. bensonlily@163.com
Huang
Na
N
Yang
Lin
L
Zheng
Da-yong
DY
Cui
Yan-zhi
YZ
Li
Ai-min
AM
Lü
Cheng-wei
CW
Zheng
Hang
H
Luo
Rong-cheng
RC
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology; D001557:Benzenesulfonates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D000077157:Sorafenib
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D009536:Niacinamide; D000077157:Sorafenib