Interventional Department, The Fourth Affiliated Hospital of China Medical University, Shenyang, P. R. China.
Department of Gastroenterology, The Fourth Affiliated Hospital of China Medical University, Shenyang, P. R. China.
J Cell Biochem. 2018 May;119(5):4050-4060. doi: 10.1002/jcb.26576. Epub 2018 Jan 19.
This study aims to investigate the influence of the Wnt/β-catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma (HCC) cells after transcatheter arterial chemoembolization (TACE) in rat models. A total of 80 rats were grouped into sham, TACE, Wnt-C59, and TACE + Wnt-C59 groups (n = 20). Ten days after model establishment, 10 rats in each group were executed to perform pathological examination and follow-up experiment, and the remaining 10 rats in each group were reared to observe the survival condition. RT-qPCR and Western blotting were applied to determine the expressions of Wnt1, β-catenin, cyclin D1, c-met, vimentin, E-cadherin, and vascular endothelial growth factor (VEGF). ELISA was performed to measure the serum alpha-fetoprotein (AFP) content of rats. Flow cytometry was used to evaluate cell apoptosis rate and transwell assay to examine cell migration and invasion. Compared with the TACE group, the Wnt-C59 and TACE + Wnt-C59 groups showed increased apoptosis and survival time (the TACE + Wnt-C59 group > the Wnt-C59 group). Compared with the sham group, the TACE + Wnt-C59 groups showed decreased cancer tissue weight and expressions of Wnt1, β-catenin, cyclin D1, vimentin, c-met, and VEGF, but increased E-cadherin expression. Compared with the TACE group, the Wnt-C59 and TACE + Wnt-C59 groups showed decreased AFP level, migration, and invasion (the TACE + Wnt-C59 group < the Wnt-C59 group). These findings indicate inhibition of the Wnt/β-catenin signaling pathway improves therapeutic effect on TACE via suppressing migration, invasion, and promoting apoptosis of transplanted HCC cells in rats.
本研究旨在探讨 Wnt/β-catenin 信号通路对大鼠模型经导管动脉化疗栓塞(TACE)后移植肝癌(HCC)细胞凋亡、迁移和侵袭的影响。将 80 只大鼠分为假手术组、TACE 组、Wnt-C59 组和 TACE+Wnt-C59 组(n=20)。模型建立 10 天后,每组处死 10 只大鼠进行病理检查和后续实验,每组剩余 10 只大鼠继续饲养观察生存状况。应用 RT-qPCR 和 Western blot 检测 Wnt1、β-catenin、cyclin D1、c-met、vimentin、E-cadherin 和血管内皮生长因子(VEGF)的表达。ELISA 法检测大鼠血清甲胎蛋白(AFP)含量。流式细胞术检测细胞凋亡率,Transwell 检测细胞迁移和侵袭。与 TACE 组相比,Wnt-C59 组和 TACE+Wnt-C59 组细胞凋亡增加,生存时间延长(TACE+Wnt-C59 组>TACE-C59 组)。与假手术组相比,TACE+Wnt-C59 组癌组织重量及 Wnt1、β-catenin、cyclin D1、vimentin、c-met 和 VEGF 表达降低,E-cadherin 表达升高。与 TACE 组相比,Wnt-C59 组和 TACE+Wnt-C59 组 AFP 水平、迁移和侵袭降低(TACE+Wnt-C59 组<TACE-C59 组)。这些结果表明,抑制 Wnt/β-catenin 信号通路可通过抑制大鼠移植 HCC 细胞的迁移、侵袭,促进其凋亡,提高 TACE 的治疗效果。