Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, PR China.
Department of Oncology, The Second Hospital of Tianjin Medical University, Tianjin, PR China.
Histol Histopathol. 2022 Jun;37(6):597-607. doi: 10.14670/HH-18-430. Epub 2022 Feb 7.
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.
前列腺癌是男性泌尿生殖系统最常见的恶性肿瘤之一。成纤维细胞激活蛋白α（FAP-α）的过表达已在广泛的肿瘤中被发现。然而，FAP-α 在前列腺癌发展中的具体机制尚未报道。
在这项研究中，实时定量 PCR（qRT-PCR）用于检测前列腺癌细胞系（PC-3、LNCaP 和 DU145）和人正常前列腺上皮细胞系 RWPE-1 中 FAP-α mRNA 的相对表达。靶向 FAP-α 的小干扰 RNA（siRNA）和表达外源性 FAP-α 的载体被转染到前列腺癌细胞（LNCaP 和 DU145）中，以研究 FAP-α 的功能。BALB/c 裸鼠被注射转染了 NC-siRNA、FAP-α-siRNA-1 或 FAP-α-siRNA-2 的 DU145 细胞。
与相邻正常组织相比，前列腺癌组织中 FAP-α 蛋白和 mRNA 水平显著增加（P<0.05）。与 FAP-α mRNA 水平高的患者相比，FAP-α mRNA 水平低的患者的生存率显著更高（χ²=5.050，log-rank P=0.025）。在 LNCaP 细胞中过表达 FAP-α 显著抑制细胞凋亡，并促进细胞侵袭和增殖。相反，在 DU145 细胞中敲低 FAP-α 表达可显著降低前列腺癌的侵袭、增殖，并促进凋亡。免疫荧光分析进一步表明，下调 FAP-α 可抑制β-连环蛋白的核转位。体内研究发现，与 NC-siRNA 组相比，FAP-α-siRNA-1 和 FAP-α-siRNA-2 组的肿瘤重量和肿瘤体积明显降低。
总之，下调 FAP-α 可抑制前列腺癌的侵袭和增殖。我们的研究为前列腺癌的靶向治疗提供了理论依据。
