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Secreted frizzled-related protein 5 suppresses aggressive phenotype and reverses docetaxel resistance in prostate cancer
  1. Qiang Xu1,
  2. Zhong Lü2,
  3. Xugang Wang2,
  4. Qingxian Zhu2,
  5. Haoran Wu2
  1. 1Department of Urology, Affiliated Hospital of Jiangsu University, Zhenjiang, China
  2. 2Department of Urology, Wujin Hospital Affiliated to Jiangsu University, Changzhou, China
  1. Correspondence to Dr Haoran Wu, Wujin Hospital Affiliated to Jiangsu University, Changzhou 213003, China; fdwhr2009{at}163.com

Abstract

Secreted frizzled-related protein 5 (SFRP5) has been reported to be downregulated in prostate cancer. However, its biological role in this malignancy has not been clarified yet. In the present study, we performed SFRP5 overexpression experiments to determine its function in prostate cancer cell growth, invasion, tumorigenesis, and docetaxel sensitivity. Our results showed that overexpression of SFRP5 significantly suppressed the proliferation and colony formation of PC-3 and DU-145 cells, compared with vector-transfected control cells. SFRP5 overexpression arrested PC-3 and DU-145 cells at G0/G1 phase and induced apoptosis. Transwell invasion assay revealed that ectopic expression of SFRP5 inhibited the invasion of PC-3 cells. Overexpression of SFRP5 resensitized docetaxel-resistant PC-3 and DU-145 cells to docetaxel, which was coupled with increased apoptosis. Mechanistically, SFRP5 overexpression blocked β-catenin nuclear translocation and transcriptional activity. In vivo studies confirmed that overexpression of SFRP5 significantly suppressed the growth of PC-3 xenograft tumors. SFRP5-transfected xenograft tumors showed a reduction in the percentage of Ki-67-positive proliferating cells and an increase in terminal deoxynucleotidyl transferasebiotin-dUTP nick end labeling-positive cells. These data suggest that SFRP5 overexpression suppresses the aggressive phenotype of prostate cancer cells and overcomes docetaxel resistance through inactivation of β-catenin signaling. Therefore, delivery of SFRP5 may offer therapeutic benefits in the treatment of prostate cancer.

  • cell proliferation
  • cancer

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Footnotes

  • Patient consent for publication Not required.

  • Contributors QXu and HWu participated in study design, data collection, and drafting of the manuscript; ZLü, XW, and QZ conducted experiments.

  • Funding This work was supported by the Changzhou Science and Technology Program (no. WS201514) and the Wujin Hospital, Affiliated to Jiangsu University, Changzhou, China.

  • Competing interests None declared.

  • Ethics approval All animal studies were approved by the Institutional Animal Care and Use Committee of Wujin Hospital Affiliated to Jiangsu University (Changzhou, China).

  • Provenance and peer review Not commissioned; externally peer reviewed.

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