Huang Xiang, Zhou Jianhua, Liu Junyan, Tang Binzhi, Zhao Fengyan, Qu Yi
Department of Urology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan 610041, P.R. China.
Department of Pediatrics, West China Second University Hospital, Chengdu, Sichuan 610041, P.R. China ; Key Laboratory of Obstetric, Gynecologic and Pediatric Diseases and Birth Defects of Ministry of Education, Sichuan University, Chengdu, Sichuan 610041, P.R. China.
Oncol Lett. 2014 Sep;8(3):1217-1221. doi: 10.3892/ol.2014.2259. Epub 2014 Jun 17.
Hypoxia-inducible factor (HIF)-1α has been reported to be associated with malignancy in a number of types of cancer. However, the role of HIF-1 α in the regulation of prostate cancer (PCa) growth has yet to be elucidated. The present study aimed to investigate the effect of HIF-1α on the biological characteristics of the PCa PC3 cell line. Full-length (fL) HIF-1α and dominant-negative (dn) HIF-1α were transfected into PC3 cells. The expression of HIF-1α and its downstream genes, including vascular endothelial growth factor (VEGF), erythropoietin (EPO) and CXC chemokine receptor 4 (CXCR4), were detected using western blot analysis. Cell proliferation, apoptosis and migration were assessed using MTT, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and Boyden chamber assays. The expression of VEGF, EPO and CXCR4 was found to be upregulated in the fL HIF-1α-transfected PC3 cells and downregulated in the dn HIF-1α-transfected PC3 cells. The overexpression of HIF-1α was observed to enhance cell proliferation and migration and decrease docetaxol-induced cell apoptosis. However, dn HIF-1α was found to attenuate cell proliferation and migration, and promote docetaxol-induced cell apoptosis. These findings indicate that HIF-1α regulates the proliferation, apoptosis and migration of PC3 cells, at least in part, by regulating the expression of its target genes, including VEGF, EPO and CXCR4. Thus, the use of HIF-1α inhibitors may be a promising therapy for the treatment of PCa.
据报道，缺氧诱导因子（HIF）-1α与多种类型癌症的恶性肿瘤相关。然而，HIF-1α在前列腺癌（PCa）生长调节中的作用尚未阐明。本研究旨在探讨HIF-1α对PCa PC3细胞系生物学特性的影响。将全长（fL）HIF-1α和显性阴性（dn）HIF-1α转染到PC3细胞中。采用蛋白质免疫印迹分析检测HIF-1α及其下游基因，包括血管内皮生长因子（VEGF）、促红细胞生成素（EPO）和CXC趋化因子受体4（CXCR4）的表达。使用MTT、末端脱氧核苷酸转移酶介导的dUTP缺口末端标记和博伊登室试验评估细胞增殖、凋亡和迁移。发现VEGF、EPO和CXCR4的表达在fL HIF-1α转染的PC3细胞中上调，而在dn HIF-1α转染的PC3细胞中下调。观察到HIF-1α的过表达增强细胞增殖和迁移，并减少多西他赛诱导的细胞凋亡。然而，发现dn HIF-1α减弱细胞增殖和迁移，并促进多西他赛诱导的细胞凋亡。这些发现表明，HIF-1α至少部分地通过调节其靶基因，包括VEGF、EPO和CXCR4的表达来调节PC3细胞的增殖、凋亡和迁移。因此，使用HIF-1α抑制剂可能是治疗PCa的一种有前景的疗法。
