Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.

  • Authors:
    • E Hosoi
    • M Hirose
    • S Hamano
    • M Morimoto
    • Y Kuroda
  • View Affiliations

  • Published online on: August 1, 1998     https://doi.org/10.3892/ijo.13.2.343
  • Pages: 343-351
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Abstract

In an attempt to identify the target protein, P-GP or mrp, of each MDR antagonist, verapamyl (Ver), dipyridamole (Dip), or cyclosporin A (Cy-A), this study was designed to compare the activity of the three afore-mentioned drugs and to test their combined effect on the cidal activity of vincristine (VCR) in five types of wild and the corresponding VCR-resistant cultured cell lines from human leukemia and lymphoma. Three of the VCR-resistant cell lines are characterized by the overexpression of mdr-1, while two cell lines overexpress mrp. We found that all three antagonists additively to synergistically enhanced the cidal activity of VCR for the five wild-type and VCR-resistant cell lines in a dose dependent manner when used singly. Combinations consisting of a 20% inhibitory concentration (IC20) of VCR plus two antagonists also showed additive to synergistic effects on both wild and VCR-resistant cell lines. It is of interest that the combined effect of IC20 VCR plus MDR antagonists on the three VCR-resistant cell lines expressing mdr-1 was significantly superior to those of the two cell lines expressing the mrp gene. These results suggest that the combined effect of MDR antagonists work better than their single use and that the MDR antagonists work more efficiently in cells showing drug resistance through mdr-1 than in those utilizing mrp.

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Aug 1998
Volume 13 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Hosoi E, Hirose M, Hamano S, Morimoto M and Kuroda Y: Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.. Int J Oncol 13: 343-351, 1998
APA
Hosoi, E., Hirose, M., Hamano, S., Morimoto, M., & Kuroda, Y. (1998). Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.. International Journal of Oncology, 13, 343-351. https://doi.org/10.3892/ijo.13.2.343
MLA
Hosoi, E., Hirose, M., Hamano, S., Morimoto, M., Kuroda, Y."Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.". International Journal of Oncology 13.2 (1998): 343-351.
Chicago
Hosoi, E., Hirose, M., Hamano, S., Morimoto, M., Kuroda, Y."Effect of MDR antagonists on the cidal activity of vincristine for cells expressing MDR-1 is superior to those expressing MRP.". International Journal of Oncology 13, no. 2 (1998): 343-351. https://doi.org/10.3892/ijo.13.2.343