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Wnt/β-catenin 信号通路对大鼠经导管动脉化疗栓塞后移植性肝癌细胞凋亡、迁移和侵袭的影响。

Effect of the Wnt/β-catenin signaling pathway on apoptosis, migration, and invasion of transplanted hepatocellular carcinoma cells after transcatheter arterial chemoembolization in rats.

机构信息

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.

出版信息

J Cell Biochem. 2018 May;119(5):4050-4060. doi: 10.1002/jcb.26576. Epub 2018 Jan 19.

Abstract

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.

摘要

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。

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