Open Access

Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment

  • Authors:
    • Elizabeth M. Freeburg
    • Alicia A. Goyeneche
    • Carlos M. Telleria
  • View Affiliations

  • Published online on: March 1, 2009     https://doi.org/10.3892/ijo_00000200
  • Pages: 743-755
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Abstract

Repopulation of cancer cells escaping lethal chemotherapy is a critical factor hindering treatment success. One strategy to inhibit tumor cell repopulation is the use of cytostatic compounds between courses of lethal chemotherapy. In this study, we tested the hypothesis that mifepristone (MF), a steroid compound with demonstrated growth inhibition activity in ovarian cancer, should be efficacious in inducing cytostasis and preventing repopulation of ovarian cancer cells if given among rounds of cisplatin (CDDP) treatment. We established an in vitro approach wherein ovarian cancer cells with high (OV2008) or low (SK-OV-3) sensitivity to CDDP were exposed to 3 (OV2008) or 2 (SK-OV-3) rounds of lethal doses of CDDP for 1 h, 12 (OV2008) or 24 (SK-OV-3) days apart. Every 4 or 8 days cell number, cell viability, cell cycle traverse, and colony-forming capacity of viable cells was analyzed. Although CDDP killed the vast majority of cells, there were remnant cells escaping CDDP lethality and repopulating the culture, as evidenced by increased cell number, improved clonogenic capacity of viable cells, and normalization of DNA synthesis. Conversely, when cells were exposed to CDDP for 1 h, and 5, 10 or 20 µM MF was present in the culture medium after CDDP removal, the number, clonogenic capacity, and DNA synthesis ability of the cells were reduced in a dose-dependent manner. The blockage by MF of post-CDDP repopulation was accompanied by a remarkable increase in the percentage of cells expressing the cell death marker cleaved poly(ADP-ribose) polymerase and the mitotic marker phospho-histone H3, suggesting that MF also potentiated CDDP lethality and that the cells likely die due to mitotic failure. In summary, this is the first study reporting that presence of cytostatic concentrations of MF after courses of lethal doses of CDDP prevents repopulation of remnant ovarian cancer cells surviving CDDP treatment.

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March 2009
Volume 34 Issue 3

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

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Spandidos Publications style
Freeburg EM, Goyeneche AA and Telleria CM: Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment. Int J Oncol 34: 743-755, 2009
APA
Freeburg, E.M., Goyeneche, A.A., & Telleria, C.M. (2009). Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment. International Journal of Oncology, 34, 743-755. https://doi.org/10.3892/ijo_00000200
MLA
Freeburg, E. M., Goyeneche, A. A., Telleria, C. M."Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment". International Journal of Oncology 34.3 (2009): 743-755.
Chicago
Freeburg, E. M., Goyeneche, A. A., Telleria, C. M."Mifepristone abrogates repopulation of ovarian cancer cells in between courses of cisplatin treatment". International Journal of Oncology 34, no. 3 (2009): 743-755. https://doi.org/10.3892/ijo_00000200