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作 者:罗赛芳 马向明 曹立瀛 LUO Saifang;MA Xiangming;CAO Liying(Department of Hepatobiliary Surgery,Kailuan General Hospital Affiliated to North China University of Science and Technology,Tangshan,Hebei 063000,China)
机构地区:[1]华北理工大学附属开滦总医院肝胆外科,河北唐山063000
出 处:《临床肝胆病杂志》2022年第9期2165-2171,共7页Journal of Clinical Hepatology
基 金:河北省2020年度医学科学研究课题计划(20201285)。
摘 要:肿瘤在有氧环境中仍然进行糖酵解以加速对肿瘤微环境中的葡萄糖摄取和产生大量乳酸,为肿瘤细胞增殖提供所需的核苷酸、脂质和蛋白质的生物分子前体,以及可抑制免疫细胞的功能而促进肿瘤细胞的转移。糖异生代谢作为糖酵解的逆反应在肝细胞癌中处于抑制状态,尤其是丙酮酸羧化酶、磷酸烯醇式丙酮酸羧激酶、果糖-1,6-二磷酸酶1和葡萄糖-6-磷酸酶4个关键限速酶的表达下调,通过促进有氧糖酵解及其分支途径而促进肝细胞癌的生长和增殖,同时也与肝细胞癌患者的总生存期和预后相关,被认为是肝细胞癌的抑制因子。基于此,本文总结了糖异生代谢关键酶在肝细胞癌发生发展中的变化及其作用机制,并分析了其在肝细胞癌中相关研究的不足和未来方向,期望为肝细胞癌的治疗提供新思路。Tumors still perform glycolysis in the aerobic environment to accelerate the uptake of glucose and produce a large amount of lactic acid in tumor microenvironment,provide biomolecular precursors of nucleotides,lipids,and proteins for tumor cell proliferation,and inhibit the function of immune cells and promote the metastasis of tumor cells in acidic environment.Gluconeogenesis,as the reverse reaction of glycolysis,is inhibited in hepatocellular carcinoma,especially the downregulated expression of the four key rate-limiting enzymes pyruvate carboxylase,phosphoenolpyruvate carboxykinase,fructose-1,6-diphosphate 1,and glucose-6-phosphatase 4,which promotes the growth and proliferation of hepatocellular carcinoma by promoting aerobic glycolysis and its branched pathways,and meanwhile,it is also associated with the overall survival time and prognosis of patients with hepatocellular carcinoma and is considered an inhibitor for hepatocellular carcinoma.Therefore,this review summarizes the changes and mechanism of action of the key enzymes of gluconeogenesis in the development and progression of hepatocellular carcinoma and analyzes the shortcomings and future directions of related research in hepatocellular carcinoma,so as to provide new ideas for the treatment of hepatocellular carcinoma.
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