[Reversion of drug-resistant hepatocellular carcinoma cell line BEL-7402/FU by sorafenib].
OBJECTIVE
To investigate the reversion of multidrug resistance of drug-resistant hepatocellular carcinoma (HCC) cell line BEL-7402/FU by sorafenib and the possible mechanisms.


METHODS
Flow cytometry was applied to detect the expression of rhodamine 123 (Rho123), immunohistochemistry was applied to observe the expression of P-glycoprotein (P-gp) on the cell membrane, the fluorescence quantitative PCR assay was applied to determine the changes of the multidrug-resistant gene mdr1 mRNA level and the Western blot assay was applied to test the changes of the expression level of the mdr1 gene product P-gp.


RESULTS
After 4 micromol/L treatment by sorafenib, Rho123 accumulation was increased by BEL-7402/FU and exocytosis was slowed down, which evidently reduced the expression of cell surface P-gp; the mdr1 mRNA level was reduced by 35.4% compared to its level prior to drug administration; the expression level of the mdr1 gene product P-gp was significantly suppressed, 14.3% fewer than that of BEL-7402/FU cells.


CONCLUSIONS
Sorafenib can inhibit the expression of the mdr1 gene product P-gp and increase the intracellular concentration of chemotherapeutic drugs, so as to reverse the multidrug resistance of HCC cells.
Wei
Li
L
Center of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China. bensonlily@163.com
Su
Ning
N
Zheng
Da-yong
DY
Cao
Meng-ran
MR
Li
Ai-min
AM
Yan
Xiao
X
Lü
Cheng-wei
CW
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*; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics; D005089:Exocytosis / Q000187:drug effects; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009536:Niacinamide / Q000031:analogs & derivatives; D010671:Phenylurea Compounds; D011725:Pyridines / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020112:Rhodamine 123 / Q000378:metabolism; D000077157:Sorafenib
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D001557:Benzenesulfonates; D010671:Phenylurea Compounds; D011725:Pyridines; D020112:Rhodamine 123; D009536:Niacinamide; D000077157:Sorafenib