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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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September-2016 Volume 49 Issue 3

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Article

Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells

  • Authors:
    • Hisashi Masuyama
    • Keiichiro Nakamura
    • Etsuko Nobumoto
    • Yuji Hiramatsu
  • View Affiliations / Copyright

    Affiliations: Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentist and Pharmaceutical Science, Okayama, Japan
  • Pages: 1211-1220
    |
    Published online on: July 6, 2016
       https://doi.org/10.3892/ijo.2016.3611
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Abstract

Epithelial ovarian cancer remains the most devastating gynecologic cancer with drug resistance and rapid recurrence. Pregnane X receptor (PXR) is a nuclear receptor that affects drug metabolism/efflux and drug-drug interaction through control of multiple drug resistance 1 (MDR1), which implies a major role in multidrug resistance, and other genes. We examined whether the inhibition of PXR-mediated pathway using siRNA interference and an antagonist for PXR could influence the paclitaxel and cisplatin cytotoxicity in ovarian cancer cells. PXR agonists, phthalate and pregnenolone had significant positive effects on cytochrome P450 (CYP) 3A4 expression and PXR-mediated transcription through the CYP3A4 promoter, whereas MDR1 expression and PXR-mediated transcription though the MDR1 promoter were significantly increased in the presence of paclitaxel or cisplatin. Downregulation of PXR suppressed the augmented MDR1 expression and PXR-mediated transcription by PXR ligands, and significantly enhanced cell growth inhibition and apoptosis in the presence of paclitaxel or cisplatin. Additionally, ketoconazole, a PXR antagonist, suppressed the augmented MDR1 expression and PXR-mediated transactivation by paclitaxel and cisplatin, and enhanced cell growth inhibition and apoptosis in their presence. In conclusion, inhibition of PXR-mediated pathways could be a novel means of augmenting sensitivity, or overcoming resistance to anticancer agents for ovarian cancer.
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Copy and paste a formatted citation
Spandidos Publications style
Masuyama H, Nakamura K, Nobumoto E and Hiramatsu Y: Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells. Int J Oncol 49: 1211-1220, 2016.
APA
Masuyama, H., Nakamura, K., Nobumoto, E., & Hiramatsu, Y. (2016). Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells. International Journal of Oncology, 49, 1211-1220. https://doi.org/10.3892/ijo.2016.3611
MLA
Masuyama, H., Nakamura, K., Nobumoto, E., Hiramatsu, Y."Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells". International Journal of Oncology 49.3 (2016): 1211-1220.
Chicago
Masuyama, H., Nakamura, K., Nobumoto, E., Hiramatsu, Y."Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells". International Journal of Oncology 49, no. 3 (2016): 1211-1220. https://doi.org/10.3892/ijo.2016.3611
Copy and paste a formatted citation
x
Spandidos Publications style
Masuyama H, Nakamura K, Nobumoto E and Hiramatsu Y: Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells. Int J Oncol 49: 1211-1220, 2016.
APA
Masuyama, H., Nakamura, K., Nobumoto, E., & Hiramatsu, Y. (2016). Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells. International Journal of Oncology, 49, 1211-1220. https://doi.org/10.3892/ijo.2016.3611
MLA
Masuyama, H., Nakamura, K., Nobumoto, E., Hiramatsu, Y."Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells". International Journal of Oncology 49.3 (2016): 1211-1220.
Chicago
Masuyama, H., Nakamura, K., Nobumoto, E., Hiramatsu, Y."Inhibition of pregnane X receptor pathway contributes to the cell growth inhibition and apoptosis of anticancer agents in ovarian cancer cells". International Journal of Oncology 49, no. 3 (2016): 1211-1220. https://doi.org/10.3892/ijo.2016.3611
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