Woodchuck p-glycoprotein found in virus-induced hepatocellular carcinomas binds anticancer drugs.
Virally-induced hepatocellular carcinomas (HCC) are intrinsically resistant to cancer chemotherapy partly due to increased expression of p-glycoprotein (pgp). In this study, we determined that pgp expressed in woodchuck HCC had binding properties were similar to the drug resistant human pgp. Pgp drug binding properties were characterized by photoaffinity labeling with the calcium channel blocker [3H]azidopine (AZD). AZD bound pgp in HCC but not in non-tumor liver samples, and binding was confirmed by competition with Adriamycin (IC50 = 10 microM) and actinomycin D (IC50 = 1 microM). In summary, WHV-induced HCC overexpress a pgp which binds anticancer drugs suggesting a common pathway for drug resistance.
Dunn
S E
SE
Laboratory of Molecular Carcinogenesis, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA. dunn1@niehs.nih.gov
Cullen
J M
JM
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D001386:Azides / Q000378:metabolism*; D001667:Binding, Competitive; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000662:veterinary*; D004095:Dihydropyridines / Q000378:metabolism*; D004317:Doxorubicin / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000662:veterinary*; D008392:Marmota
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000345:Affinity Labels; D000970:Antineoplastic Agents; D001386:Azides; D004095:Dihydropyridines; C041130:azidopine; D004317:Doxorubicin