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Characterization of an etoposide-resistant human ovarian cancer cell line

  • Original Articles
  • Etoposide, Multidrugresistance, Topoisomerase
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Abstract

Etoposide (VP-16) is one of the most important anticancer agents available and is used in many chemotherapeutic regimens. To characterize resistance to this drug, we established a VP-16-resistant human ovarian cancer cell line, SKOV3/VP, by continuous stepwise exposure of SKOV3 cells to VP-16. The degree of resistance to VP-16 of SKOV3/VP was about 25 times that of the parent cell line (SKOV3), and SKOV3/VP showed crossresistance to teniposide, adriamycin, CPT-11, and vincristine. The accumulation of [3H]-VP-16 observed in SKOV3/VP cells was about half that seen in SKOV3 cells, and the accumulation of Adriamycin by this resistant cell line was also lower than that of its parent. Overexpression of neither the multidrug resistance genemdr-1, the multidrug-resistance-associated protein (mrp) gene, nor P-glycoprotein was detected using reverse transcriptase-polymerase chain reaction analysis and flow cytometry with MRK-16, a monoclonal antibody against P-glycoprotein. The topoisomerase II activity of nuclear extracts from SKOV3/VP cells was lower than that from the parental cells, as was the amount of DNA topoisomerase II, demonstrated by immunoblotting. These results suggest that the mechanism responsible for the multidrug resistance of this cell line may be attributable to changes on its DNA topoisomerase II and to its reduced accumulation of the drugs as compared with the parental line SKOV3.

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Authors and Affiliations

  1. Pharmacology Division, National Cancer Center Research Institute, 1-1 Tsukiji 5-chome, Chou-ku, 104, Tokyo, Japan

    Naohiro Kubota, Kazuto Nishio, Yuichiro Takeda, Tohru Ohmori, Yasunori Funayama, Hayato Ogasawara, Tatsuo Ohira, Hiroshi Kunikane & Nagahiro Saijo

  2. Department of Obstetrics and Gynecology, Jikei University School of Medicine, 104, Tokyo, Japan

    Naohiro Kubota & Yoshiteru Terashima

Authors
  1. Naohiro Kubota
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  2. Kazuto Nishio
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  3. Yuichiro Takeda
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  4. Tohru Ohmori
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  5. Yasunori Funayama
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  6. Hayato Ogasawara
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  7. Tatsuo Ohira
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  8. Hiroshi Kunikane
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  9. Yoshiteru Terashima
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  10. Nagahiro Saijo
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Kubota, N., Nishio, K., Takeda, Y. et al. Characterization of an etoposide-resistant human ovarian cancer cell line. Cancer Chemother. Pharmacol. 34, 183–190 (1994). https://doi.org/10.1007/BF00685075

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  • DOI: https://doi.org/10.1007/BF00685075

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