Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer

  • Authors:
    • Yun‑Fei Li
    • Hui‑Hua Ji
    • Zheng‑Long Zhang
    • Tao‑Tao Zhang
    • Wei Gan
    • Shao‑Feng Zhang
  • View Affiliations

  • Published online on: June 8, 2017     https://doi.org/10.3892/ol.2017.6357
  • Pages: 1748-1756
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It has been demonstrated that docetaxel (DTX) may improve the overall survival of patients with castration-resistant prostate cancer (CRPC). However, its effectiveness is limited with time, and tumor escape is eventually inevitable. DTX resistance is the main reason for the failure of chemotherapy for CRPC. In the present study, the expression status of multidrug resistance protein 4 (MRP4) in DTX‑resistant prostate cancer cells was investigated, and it was explored whether anti‑androgen treatment may inhibit MRP4 expression and overcome DTX resistance. DTX‑resistant C4‑2/D cells were established by exposing DTX‑sensitive C4‑2/S cells to gradually increasing concentrations of DTX. MRP4 gene expression and the effect of androgen signaling on its expression were assessed by reverse transcription‑polymerase chain reaction and western blotting. Intracellular and extracellular concentrations of DTX were detected by high‑performance liquid chromatography. Anti‑androgen treatment effects on DTX sensitivity were determined by a clonogenic test and an MTT cytotoxicity assay. MRP4 was overexpressed in C4‑2/D cells, while its expression was barely detectable in C4‑2/S cells. MRP4 expression levels were elevated in C4‑2/D cells by dihydrotestosterone, whereas they were blocked by anti‑androgen bicalutamide (BKL) treatment. Intracellular and extracellular DTX concentrations in C4‑2/D cells were associated with MRP4 levels. The downregulation of MRP4 by BKL increased the intracellular concentration of DTX in C4‑2/D cells and re‑sensitized C4‑2/D cells to DTX. These results indicated that overexpression of MRP4 mediates acquired DTX resistance, and suggest that targeting MRP4 expression by anti‑androgen treatment may reverse DTX‑resistant prostate cancer cells to DTX chemotherapy.
View Figures
View References

Related Articles

Journal Cover

August-2017
Volume 14 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Li YF, Ji HH, Zhang ZL, Zhang TT, Gan W and Zhang SF: Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer. Oncol Lett 14: 1748-1756, 2017
APA
Li, Y., Ji, H., Zhang, Z., Zhang, T., Gan, W., & Zhang, S. (2017). Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer. Oncology Letters, 14, 1748-1756. https://doi.org/10.3892/ol.2017.6357
MLA
Li, Y., Ji, H., Zhang, Z., Zhang, T., Gan, W., Zhang, S."Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer". Oncology Letters 14.2 (2017): 1748-1756.
Chicago
Li, Y., Ji, H., Zhang, Z., Zhang, T., Gan, W., Zhang, S."Targeting MRP4 expression by anti-androgen treatment reverses MRP4-mediated docetaxel resistance in castration-resistant prostate cancer". Oncology Letters 14, no. 2 (2017): 1748-1756. https://doi.org/10.3892/ol.2017.6357