[Reversion of drug-resistant hepatocellular carcinoma cell line BEL-7402/FU by sorafenib].
摘要
AIM: 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. CONCLUSION: 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.