GINS1对肝细胞癌糖酵解、上皮间质转化和血管生成的影响

摘要/Abstract

摘要： 目的探究GINS1对肝细胞癌(HCC)糖酵解、上皮间质转化(EMT)和血管生成的影响。方法对HCC细胞系MHCC97H和Hep3B细胞分别进行GINS1敲低处理(shGINS1-NC、shGINS1),蛋白质免疫印迹检测糖酵解相关蛋白、EMT相关蛋白表达水平;EDU实验和克隆形成实验检测各组细胞增殖活性;划痕实验和Transwell实验检测各组细胞转移活性,与人脐静脉血管内皮细胞HUVEC共培养以检测肿瘤血管生成能力。构建12只裸鼠HCC荷瘤模型,并分为shGINS1-NC-nude、shGINS1-nude,每组各6只,观察两组裸鼠肿瘤生长情况,并检测糖酵解相关蛋白和EMT相关蛋白表达水平的差异。结果与shGINS1-NC组相比,shGINS1组细胞GLUT1、HK2、LDHA、Vimentin、N-cadherin蛋白水平降低,E-cadherin、ZO-1蛋白水平升高,细胞增殖、转移和血管生成能力均受到显著抑制(均P<0.05)。与shGINS1-NC-nude组相比,shGINS1-nude组裸鼠肿瘤体积和质量均减小,HCC肿瘤组织GLUT1、HK2、LDHA、Vimentin、N-cadherin蛋白水平降低,E-cadherin、ZO-1蛋白水平升高(均P<0.05)。结论下调GINS1表达水平可以抑制HCC细胞糖酵解、EMT、血管生成和转移。

关键词: GINS1, 肝细胞癌, 糖酵解, 上皮间质转化, 血管生成

Abstract: Objective To investigate the effects of GINS1 on glycolysis, epithelial-mesenchymal transition (EMT), and angiogenesis in hepatocellular carcinoma (HCC). Methods GINS1 knockdown was performed in HCC cell lines MHCC97H and Hep3B cells (shGINS1-NC, shGINS1), and the expression levels of glycolysis-related proteins and EMT-related proteins were detected by Western blot. Cell proliferation activity was detected by EDU assay and colony formation assay, and cell metastasis activity was detected by scratch assay and Transwell assay. HUVEC cells were co-cultured to detect tumor angiogenesis ability. Twelve nude mice HCC xenograft models were constructed and divided into shGINS1-NC-nude and shGINS1-nude groups, with 6 mice in each group. The tumor volume of the two groups of nude mice were observed, and the expression level of glycolysis-related proteins and EMT-related proteins were detected. Results Compared with the shGINS1-NC group, the protein levels of GLUT1, HK2, LDHA, Vimentin, and N-cadherin were decreased, and the protein levels of E-cadherin and ZO-1 were increased in the shGINS1 group, and the cell proliferation, metastasis, and angiogenesis abilities were significantly inhibited (all P<0.05). Compared with the shGINS1-NC-nude group, the tumor volume and weight were reduced, and the protein levels of GLUT1, HK2, LDHA, Vimentin, and N-cadherin were decreased, and the protein levels of E-cadherin and ZO-1 were increased in the shGINS1-nude group (all P<0.05). Conclusion Downregulation of GINS1 expression level can inhibit HCC cell glycolysis, EMT, angiogenesis and metastasis.

Key words: GINS1, Hepatocellular carcinoma, Glycolysis, Epithelial-mesenchymal transition, Angiogenesis

吕瑜清, 陈思. GINS1对肝细胞癌糖酵解、上皮间质转化和血管生成的影响[J]. 肝脏, 2026, 31(4): 539-544.

LV Yu-qing, CHEN Si. The effect of GINS1 on glycolysis, epithelial-mesenchymal transition and angiogenesis in hepatocellular carcinoma[J]. Chinese Hepatolgy, 2026, 31(4): 539-544.

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