Qu Bo, Liu Bing-Rong, DU Ya-Ju, Chen Jing, Cheng Yan-Qiu, Xu Wei, Wang Xin-Hong
Department of Gastroenterology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Oncol Lett. 2014 Apr;7(4):1175-1178. doi: 10.3892/ol.2014.1828. Epub 2014 Jan 27.
The Wnt/β-catenin signaling pathway plays a key role during hepatocellular carcinoma (HCC) genesis and development. The present study aimed to investigate the effects of the Wnt/β-catenin signaling pathway on the expression of angiogenic growth factors involved in HCC. The HCC HepG2 cell line was transfected with small interfering RNA (siRNA) against β-catenin. After 72 and 96 h, protein was extracted and the expression levels of β-catenin, matrix metalloproteinase (MMP)-2, MMP-9, vascular endothelial growth factor (VEGF)-A, VEGF-C and basic fibroblast growth factor (bFGF) were detected by western blot analysis. β-catenin protein expression was inhibited at both time points. Notably, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF protein expression levels decreased at 72 h and then increased at 96 h after transfection. Our results demonstrated that in HCC cells, the Wnt/β-catenin signaling pathway may regulate the protein expression of the angiogenic factors, MMP-2, MMP-9, VEGF-A, VEGF-C and bFGF. These proteins were downstream of β-catenin signaling and were also regulated by other factors. In conclusion, the Wnt/β-catenin signaling pathway may contribute to the regulation of HCC angiogenesis, infiltration and metastasis through regulating the expression of these angiogenic factors.
Wnt/β-连环蛋白信号通路在肝细胞癌（HCC）的发生和发展过程中起关键作用。本研究旨在探讨Wnt/β-连环蛋白信号通路对HCC中血管生成生长因子表达的影响。用针对β-连环蛋白的小干扰RNA（siRNA）转染HCC HepG2细胞系。72小时和96小时后，提取蛋白质，通过蛋白质印迹分析检测β-连环蛋白、基质金属蛋白酶（MMP）-2、MMP-9、血管内皮生长因子（VEGF）-A、VEGF-C和碱性成纤维细胞生长因子（bFGF）的表达水平。在两个时间点β-连环蛋白的蛋白表达均受到抑制。值得注意的是，转染后72小时MMP-2、MMP-9、VEGF-A、VEGF-C和bFGF的蛋白表达水平下降，然后在96小时升高。我们的结果表明，在HCC细胞中，Wnt/β-连环蛋白信号通路可能调节血管生成因子MMP-2、MMP-9、VEGF-A、VEGF-C和bFGF的蛋白表达。这些蛋白是β-连环蛋白信号的下游，也受其他因子调控。总之，Wnt/β-连环蛋白信号通路可能通过调节这些血管生成因子的表达，参与HCC血管生成、浸润和转移的调控。
