Secreted frizzled-related protein 5 suppresses aggressive phenotype and reverses docetaxel resistance in prostate cancer.

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.

• Authors: Qiang Xu, Zhong Lü, Xugang Wang, Qingxian Zhu, Haoran Wu
• Journal: Journal of investigative medicine : the official publication of the American Federation for Clinical Research (J Investig Med) Vol. 67 Issue 6 Pg. 1009-1017 (08 2019) ISSN: 1708-8267 [Electronic] England
• PMID: 30787036 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.

Chemical References

• Adaptor Proteins, Signal Transducing
• SFRP5 protein, human
• beta Catenin
• Docetaxel

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Apoptosis
• Carcinogenesis (pathology)
• Cell Cycle Checkpoints
• Cell Line, Tumor
• Cell Proliferation
• Docetaxel (therapeutic use)
• Drug Resistance, Neoplasm
• G1 Phase
• Humans
• Male
• Mice, Nude
• Neoplasm Invasiveness
• Phenotype
• Prostatic Neoplasms (drug therapy, pathology)
• Resting Phase, Cell Cycle
• Signal Transduction
• beta Catenin (metabolism)