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. 1997 Jan;88(1):88-96.
doi: 10.1111/j.1349-7006.1997.tb00306.x.

Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins

S Wakusawa  1 , S Nakamura, K Miyamoto
Affiliations

Establishment by adriamycin exposure of multidrug-resistant rat ascites hepatoma AH130 cells showing low DT-diaphorase activity and high cross resistance to mitomycins

S Wakusawa et al. Jpn J Cancer Res. 1997 Jan.

Abstract

A resistant subline (AH130/5A) selected from rat hepatoma AH130 cells after exposure to adriamycin (ADM) showed remarkable resistance to multiple antitumor drugs, including mitomycin C (MMC) and porfiromycin (PFM). PFM, vinblastine (VLB), and ADM accumulated in AH130/5A far less than in the parent AH130 (AH130/P) cells. AH130/5A cells showed overexpression of P-glycoprotein (PGP), an increase in glutathione S-transferase activity, and a decrease in DT-diaphorase and glutathione peroxidase activity. The resistance to MMC and VLB of AH130/5A cells was partly reversed by H-87, an inhibitor of PGP. Buthionine sulfoximine, an inhibitor of glutathione synthase, did not affect the action of MMC. tert-Butylhydroquinone induced DT-diaphorase activity, increased PFM uptake, and enhanced the growth-inhibitory action of MMC in AH130/5A cells. Dicumarol, an inhibitor of DT-diaphorase, decreased PFM uptake and reduced the growth-inhibitory action of MMC in AH130/P cells. These results indicated that the adriamycin treatment of hepatoma cells caused multifactorial multidrug resistance involving a decrease in DT-diaphorase activity.

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References

    1. ) Tsuruo , T. , Iida‐Saito , H. , Kawabata , H. , Ohhara , H. , Hamada , H. and Utakoji , T.Characteristics of resistance to adriamycin in human myelogenous leukemia K562 resistant to Adriamycin and in isolated clones . Jpn. J. Cancer Res. , 77 , 682 – 692 ( 1986. ). - PubMed
    1. ) Hagiwara , M. , Wakusawa , S. , ‐Miyamoto , K. and Hidaka , H.Obviation of drug resistance and affinity purification of P‐glycoprotein by isoquinolinesulfonamides . Cancer Lett. , 60 , 103 – 107 ( 1991. ). - PubMed
    1. ) Mizuno , K. , Furuhashi , Y. , Maeda , O. , Iwata , M. , Misawa , T. , Kawai , M. , Kano , T. and Tomoda , Y.Mitomycin C cross‐resistance induced by adriamycin in human ovarian cancer cells in vitro . Cancer Chemother. Pharmacol , 26 , 333 – 339 ( 1990. ). - PubMed
    1. ) Chen , Y. N. , Mickley , L. A. , Schwartz , A. M. , Acton , E. M. , Hwang , J. L. and Fojo , A. T.Characterization of adriamycin‐resistant human breast cancer cells which display overexpression of a novel resistance‐related membrane protein . J. Biol. Chem. , 265 , 10073 – 10080 ( 1990. ). - PubMed
    1. ) Scheper , R. J. , Broxtermann , H. J. , Scheffer , G. L. , Kaaijk , P. , Dalton , W. S. , van Heijinigen , T. H. M. , van Kalken , C. K. , Slovak , M. L. , de Vries , E. G. E. , van der Valk , P. , Meijer , C. J.L. M. and Pinedo , H. M.Overexpression of a Mr110,000 vesicular protein in non‐P‐glycoprotein‐mediated multidrug resistance . Cancer Res. 53 , 1475 – 1479 ( 1993. ). - PubMed

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