Establishment of a 5-DFUR-resistant human hepatocellular carcinoma cell model and preliminary study of the mechanisms of the drug resistance / 南方医科大学学报

ABSTRACT

<p><b>OBJECTIVE</b>To establish a multidrug-resistant hepatocellular carcinoma cell line BEL-7402/5-deoxy-5-fluorouridine (5'-DFUR) and study the mechanisms of the drug resistance.</p><p><b>METHODS</b>BEL-7402/5'-DFUR cell line was induced by pulse therapy combined with continuous stepwise exposure to 5'-DFUR in vitro. The multidrug resistance of BEL-7402/5'-DFUR cell line to the antitumor agents was evaluated by MTT assay. The distribution of the cell cycle, the expressions of P-gp, bcl-2 and GST-pi were detected by flow cytometry.</p><p><b>RESULTS</b>The established BEL-7402/5'-DFUR cell line was resistant to multiple antitumor agents, with IC(50) of 5'-DFUR 12.9 times higher than that of the parental cell line 7204. The BEL-7402/5'-DFUR cells in S phase decreased while those in G(1) and G(2) phase increased, with significantly increased expressions of P-gp and bcl-2 but stable expression of GST-pi.</p><p><b>CONCLUSION</b>Compared with its parent cell line BEL-7402, the multidrug resistant cell line BEL-7402/5'-DFUR has a 12.9-fold increase in IC(50) of 5'-DFUR with decreased drug accumulation and altered cell cycle distribution. The multi-drug resistance of this cell line is closely related to the overexpression of P-gp and bcl-2.</p>