Fibroblast activation protein-alpha knockdown suppresses prostate cancer cell invasion and proliferation.

Abstract

Prostate cancer is one of the most common malignant tumors of the male genitourinary system. Fibroblast activation protein alpha (FAP-α) overexpression has been shown to occur in a wide range of tumors. However, the specific mechanism of FAP-α in the development of prostate cancer has not been reported. In this study, real-time quantitative PCR (qRT-PCR) was used to detect the relative expression of FAP-α mRNA in prostate cancer cell lines (PC-3, LNCaP, and DU145) and human normal prostate epithelial cell line RWPE-1. Small interfering RNA (siRNA) targeting FAP-α and vectors expressing exogenous FAP-α were transfected to prostate cancer cells (LNCaP and DU145) to investigate the function of FAP-α. BALB/c nude mice were injected with DU145 cells which were transfected with NC-siRNA, FAP-α-siRNA-1, or FAP-α-siRNA-2. Compared to adjacent normal tissues, FAP-α protein and mRNA levels in prostate cancer tissues increased significantly (P<0.05). Compared to patients with high FAP-α mRNA levels, patients with low FAP-α mRNA levels had a significantly higher survival rate (χ²=5.050, log-rank P=0.025). Overexpression of FAP-α in LNCaP cells markedly inhibited cell apoptosis, and promoted cell invasion and proliferation. In contrast, knockdown of FAP-α expression in DU145 cells can significantly reduce invasion, proliferation, and promote apoptosis in prostate cancer. Immunofluorescence assay further indicated that down-regulation of FAP-α could suppress the nuclear translocation of β-catenin. An in vivo study found that compared with the NC-siRNA group, the tumor weight and tumor volume in the FAP-α-siRNA-1 and FAP-α-siRNA-2 groups were significantly decreased. In conclusion, down-regulation of FAP-α can inhibit the invasion and proliferation of prostate cancer. Our study provides a theoretical basis for the targeted treatment of prostate cancer.