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Human pregnane X receptor and resistance to chemotherapy in prostate cancer

Yakun Chen1, Yong Tang, Man-Tzu Wang

  • 1Department of Medical Microbiology, Immunology and Cell Biology, Southern Illinois University, School of Medicine and Simmons Cooper Cancer Institute, Springfield, IL 62794-9626, USA.

Cancer Research
|November 3, 2007
PubMed

Insights

Human pregnane X receptor (hPXR) activation increases resistance to chemotherapy drugs like Taxol and vinblastine in prostate cancer cells. Inhibiting hPXR enhances sensitivity to these treatments, suggesting hPXR is a key factor in drug resistance.

Area of Science:

  • Molecular biology
  • Cancer research
  • Pharmacology

Background:

  • Chemotherapy resistance is a major challenge in prostate cancer treatment.
  • The human pregnane X receptor (hPXR) regulates drug metabolism and transporters, and its role in prostate cancer drug resistance is unclear.

Purpose of the Study:

  • To investigate the role of hPXR in prostate cancer chemoresistance.
  • To determine if hPXR activation or inhibition affects sensitivity to chemotherapeutic agents.

Main Methods:

  • Detected hPXR expression in prostate tissues.
  • Used hPXR agonist SR12813 to treat PC-3 cells, assessing PXR translocation, CYP3A4 and MDR1 expression, and cell viability/survival.
  • Knocked down hPXR using short hairpin RNAs in PC-3 cells and evaluated effects on CYP3A4 promoter activity and drug sensitivity.

Main Results:

  • SR12813 treatment caused PXR nuclear translocation and increased CYP3A4 and MDR1 expression in PC-3 cells.
  • hPXR activation enhanced resistance to Taxol and vinblastine.
  • hPXR knockdown decreased CYP3A4 promoter activity and increased sensitivity to Taxol and vinblastine.

Conclusions:

  • hPXR activation contributes to prostate cancer cell resistance to chemotherapeutics.
  • hPXR is a potential therapeutic target for overcoming chemoresistance in prostate cancer.

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