Open Access

CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro

  • Authors:
    • Zhuangyan Zhu
    • Yaqin Mu
    • Caixia Qi
    • Jian Wang
    • Guoping Xi
    • Juncheng Guo
    • Ruoran Mi
    • Fuxi Zhao
  • View Affiliations

  • Published online on: December 16, 2014     https://doi.org/10.3892/ijmm.2014.2041
  • Pages: 340-348
  • Copyright: © Zhu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Ovarian cancer (OC) is the most frequent cause of mortality among gynecological malignancies, with a 5-year survival rate of approximately 30%. The standard regimen for OC therapy includes a platinum agent combined with a taxane, to which the patients frequently acquire resistance. Resistance arises from the oxidation of anticancer drugs by CYP1B1, a cytochrome P450 enzyme overexpressed in malignant OC. The aim of the present study was to determine the role of CYP1B1 expression in the drug resistance of OC to the taxane, paclitaxel (PTX). Immunohistochemical staining was used to assess CYP1B1 expression in a panel of ovarian samples (53 primary cancer samples, 14 samples of metastastic cancer, 30 benign tumor samples and 19 normal tissue samples). Semi-quantitative RT-PCR was also performed to determine CYP1B1 expression in several OC cell lines. Finally, we used proliferation and toxicity assays, as well as a mouse xenograft model using nude mice to determine whether α-naphthoflavone (ANF), a CYP1B1 specific inhibitor, reduces resistance to PTX. CYP1B1 was overexpressed in the samples from primary and metastatic loci of epithelial ovarian cancers. In some cell lines, PTX induced CYP1B1 expression, which resulted in drug resistance. Exposure to ANF reduced drug resistance and enhanced the sensitivity of OC cells to PTX in vitro and in vivo. The expression profile of CYP1B1 suggests that it has the potential to be a useful diagnostic marker and prognostic factor for malignant OC. The inhibition of CYP1B1 expression by specific agents may provide a novel therapeutic strategy for the treatment of patients resistant to PTX and may improve the prognosis of these patients.
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February-2015
Volume 35 Issue 2

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Zhu Z, Mu Y, Qi C, Wang J, Xi G, Guo J, Mi R and Zhao F: CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro. Int J Mol Med 35: 340-348, 2015.
APA
Zhu, Z., Mu, Y., Qi, C., Wang, J., Xi, G., Guo, J. ... Zhao, F. (2015). CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro. International Journal of Molecular Medicine, 35, 340-348. https://doi.org/10.3892/ijmm.2014.2041
MLA
Zhu, Z., Mu, Y., Qi, C., Wang, J., Xi, G., Guo, J., Mi, R., Zhao, F."CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro". International Journal of Molecular Medicine 35.2 (2015): 340-348.
Chicago
Zhu, Z., Mu, Y., Qi, C., Wang, J., Xi, G., Guo, J., Mi, R., Zhao, F."CYP1B1 enhances the resistance of epithelial ovarian cancer cells to paclitaxel in vivo and in vitro". International Journal of Molecular Medicine 35, no. 2 (2015): 340-348. https://doi.org/10.3892/ijmm.2014.2041