Characterization of naturally acquired multiple-drug resistance of Yoshida rat ascites hepatoma AH66 cell line
Miyamoto, K.; Wakabayashi, D.; Minamino, T.; Nomura, M.; Wakusawa, S.; Nakamura, S.
Anticancer Research 16(3a): 1235-1240
1996
ISSN/ISBN: 0250-7005 PMID: 8702243 Document Number: 459705
Characteristics of multiple-drug resistance of rat ascites hepatoma AH66, a cell line induced by dimethylaminoazobenzene and established as a transplantable tumor, were compared with those of AH66F, a drug sensitive line obtained from AH66. The AH66 cell line was resistant to vinblastine, adriamycin, SN-38 an active form of camptothesine, etoposide, and chlorambucil by 10-fold or more than the AH66F cell line. The resistance of AH66 cells to vinblastine, adriamycin, and SN-38 was closely related to P-glycoprotein overexpression in the plasma membrane, because the resistance was significantly inhibited by verapamil AH66 cells contained much glutathione and had a high activity of glutathione S-transferase P-form (GST-P), compared with AH66F cells, and resistance to chlorambucil was decreased by treatment with buthionine sulfoximine, an inhibitor of glutathione synthesis. AH66 cells have a similar topoisomerase I activity, but about 6 times lower topoisomerase II activity than AH66F cells. Therefore, the resistance to etoposide and a part of the resistance to adriamycin of AH66 cells seems to depend upon this low topoisomerase II activity. These results, show that the AH66 cell line has high multiple-drug resistance compared with the AH66F cell line, by several mechanisms. Consequently, the AH66 and AH66F cell lines are useful to study naturally acquired multiple-drug resistance of hepatomas.