Non‐P‐glycoprotein‐mediated Atypical Multidrug Resistance in a Human Bladder Cancer Cell Line

Seiji Naito, Shuji Hasegawa, Akira Yokomizo, Hirofumi Koga, Shuji Kotoh, Michihiko Kuwano, Joichi Kumazawa

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Abstract

A human bladder cancer cell line resistant to adriamycin (ADM), T24/ADM9 has been established in vitro by exposing T24 parent cells to progressively higher concentrations of the drug over a period of 12 months. The T24/ADM9 cells were found to be 9 times more resistant to ADM than the T24 parent, and showed various degrees of cross‐resistance to an ADM derivative, vinca alkaloids and a DNA topoisomerase II (Topo ID‐targeting agent, etoposide. No significant difference was observed in the cellular accumulation of ADM between the T24/ADM9 and T24 parent cells. A Northern blot analysis showed an overexpression of multidrug resistance‐associated protein (MRP) mRNA, but no overexpression of multidrug resistance‐1 (MDR1) mRNA was observed in the T24/ADM9 cells. A flow cytometric analysis showed that the MDR1 gene product, P‐glycoprotein (Pgp), is not expressed on the T24/ADM9 cells. T24/ADM9 showed approximately the parental level of DNA Topo II catalytic activity. In Western blot and Northern blot analyses, however, the cellular level of DNA topo II was apparently much lower in T24/ADM9 than in the T24 parent. Thus, these results suggest that a decreased cellular level of DNA Topo II and an overexpression of MRP gene may be responsible for the expression of an MDR phenotype in the T24/ADM9 cells and that such non‐Pgp‐mediated, atypical MDR may develop in bladder cancer treated with chemotherapy including ADM.

Original languageEnglish
Pages (from-to)1112-1118
Number of pages7
JournalJapanese Journal of Cancer Research
Volume86
Issue number11
DOIs
Publication statusPublished - Jan 1 1995

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Multiple Drug Resistance
Urinary Bladder Neoplasms
Doxorubicin
Cell Line
Northern Blotting
DNA
Vinca Alkaloids
Type II DNA Topoisomerase
Messenger RNA
Etoposide
Proteins
Western Blotting
Phenotype
Drug Therapy
Pharmaceutical Preparations
Genes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Non‐P‐glycoprotein‐mediated Atypical Multidrug Resistance in a Human Bladder Cancer Cell Line. / Naito, Seiji; Hasegawa, Shuji; Yokomizo, Akira; Koga, Hirofumi; Kotoh, Shuji; Kuwano, Michihiko; Kumazawa, Joichi.

In: Japanese Journal of Cancer Research, Vol. 86, No. 11, 01.01.1995, p. 1112-1118.

Research output: Contribution to journalArticle

Naito, S, Hasegawa, S, Yokomizo, A, Koga, H, Kotoh, S, Kuwano, M & Kumazawa, J 1995, 'Non‐P‐glycoprotein‐mediated Atypical Multidrug Resistance in a Human Bladder Cancer Cell Line', Japanese Journal of Cancer Research, vol. 86, no. 11, pp. 1112-1118. https://doi.org/10.1111/j.1349-7006.1995.tb03028.x
Naito, Seiji ; Hasegawa, Shuji ; Yokomizo, Akira ; Koga, Hirofumi ; Kotoh, Shuji ; Kuwano, Michihiko ; Kumazawa, Joichi. / Non‐P‐glycoprotein‐mediated Atypical Multidrug Resistance in a Human Bladder Cancer Cell Line. In: Japanese Journal of Cancer Research. 1995 ; Vol. 86, No. 11. pp. 1112-1118.
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