[Establishment of a 5-DFUR-resistant human hepatocellular carcinoma cell model and preliminary study of the mechanisms of the drug resistance].
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Tang
Hao
H
Department of Hepatobiliary Surgery, 187 Central Hospital of PLA, Haikou 571159, China.
Liang
Ping
P
Li
Rong-Ping
RP
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005467:Floxuridine / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000964:Antimetabolites, Antineoplastic; D019253:Proto-Oncogene Proteins c-bcl-2; D005467:Floxuridine; D005982:Glutathione Transferase; C025034:doxifluridine