Liu Jing, Li Guangbing, Liu Dejie, Liu Jun
Department of Ophthalmology, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China.
Department of Liver Transplantation and Hepatobiliary Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
Mol Med Rep. 2014 Apr;9(4):1289-92. doi: 10.3892/mmr.2014.1928. Epub 2014 Jan 30.
Hepatocellular carcinoma (HCC) is a primary cancer of the liver. Target therapy may improve prognosis of HCC. In the present study, we evaluated the inhibition of the Wnt/β-catenin pathway as a potential therapeutic approach. HepG2 cells were treated with the β-catenin inhibitor FH535. β-catenin protein expression was semi-quantitatively assessed using western blot analysis. Cell proliferation was examined with a 3‑(4,5-dimethyl-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. The mRNA expression of nitric oxide synthase (iNOS) was detected by reverse transcription polymerase chain reaction. The Griess assay was used to determine nitric oxide (NO) concentration. FH535 inhibited the proliferation of HepG2 cells and decreased β-catenin protein expression. mRNA expression of iNOS, a target gene of the Wnt/β-catenin pathway, was decreased in FH535‑treated HepG2 cells compared to the control group. NO production was also reduced by FH535. In conclusion, the β-catenin inhibitor FH535 may inhibit HCC cell proliferation via downregulation of the Wnt/β-catenin pathway. Thus, targeting this pathway may be useful in HCC therapy.
肝细胞癌（HCC）是肝脏的原发性癌症。靶向治疗可能会改善HCC的预后。在本研究中，我们评估了抑制Wnt/β-连环蛋白通路作为一种潜在的治疗方法。用β-连环蛋白抑制剂FH535处理HepG2细胞。使用蛋白质印迹分析半定量评估β-连环蛋白的蛋白表达。用3-（4,5-二甲基-2-基）-5-（3-羧基甲氧基苯基）-2-（4-磺基苯基）-2H-四唑盐（MTS）试验检测细胞增殖。通过逆转录聚合酶链反应检测一氧化氮合酶（iNOS）的mRNA表达。使用格里斯试验测定一氧化氮（NO）浓度。FH535抑制HepG2细胞的增殖并降低β-连环蛋白的蛋白表达。与对照组相比，在FH535处理的HepG2细胞中，Wnt/β-连环蛋白通路的靶基因iNOS的mRNA表达降低。FH535也降低了NO的产生。总之，β-连环蛋白抑制剂FH535可能通过下调Wnt/β-连环蛋白通路来抑制HCC细胞增殖。因此，靶向该通路可能对HCC治疗有用。
