大黄素通过糖酵解代谢途径抑制胃癌细胞FOXD1表达的研究  

Inhibition of FOXD1 Gene Expression in Gastric Cancer Cells by Emodin through Glycolytic Metabolism Pathway

作　　者：刘春宏 钱薇 张飞 朱艳秋 刘杰民[4] 褚明亮 LIU Chunhong;QIAN Wei;ZHANG Fei;ZHU Yanqiu;LIU Jiemin;CHU Mingliang(First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001;Graduate School,Guizhou University of Traditional Chinese Medicine,Guiyang 550002;Department of Clinical Laboratory,First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guiyang 550001;*Department of Endoscopy,Guizhou Provincial People's Hospital,Guiyangg550002)

机构地区：[1]贵州中医药大学第一附属医院,贵阳550001 [2]贵州中医药大学研究生院,贵阳550002 [3]贵州中医药大学第一附属医院检验科,贵阳550001 [4]贵州省人民医院消化内镜科,贵阳550002

出　　处：《中药药理与临床》2025年第1期90-94,共5页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目(编号:81560088、82060850);贵州省科技厅基金项目(编号:黔科合基础-ZK[2022]一般520);贵州省高层次创新型人才基金项目(编号:黔科合平台人才[2020]6016-2);贵州省卫健委基金项目(编号:gzwkj2021-056、gzwkj2023-453);贵阳市科技局基金项目(编号:筑科合同[2022]-4-3-3);贵州省高等学校工程研究中心项目(编号:黔教技[2023]037号)。

摘　　要：目的:探讨大黄素通过糖酵解代谢途径抑制胃癌细胞致癌基因叉头框蛋白D1(FOXD1)表达的可能机制。方法:以大黄素干预胃癌MGC803细胞,运用CCK8试验、划痕试验、Transwell小室试验检测细胞生物学特性的变化;葡萄糖和乳酸试剂盒检测细胞代谢的变化。基于基因表达水平值的交互式分析平台(GEPIA)数据库分析己糖激酶Ⅱ(HK2)、乳酸脱氢酶A(LDHA)和FOXD1在胃癌组织中的表达情况。蛋白免疫印迹(Western blot)法检测大黄素对HK2、LDHA和FOXD1蛋白的表达影响。添加丙酮酸,检测是否可逆转大黄素的抑制作用。结果:与空白对照组比较,大黄素20、30μmol/L组胃癌MGC803细胞的增殖、迁移和侵袭能力明显降低,葡萄糖的消耗及乳酸的生成明显降低(P<0.05)。GEPIA数据库分析显示与正常患者胃组织比较,胃癌组织中HK2、LDHA和FOXD1的表达明显上调(P<0.05)。与空白对照组比较,大黄素组对胃癌MGC803细胞的HK2和FOXD1蛋白表达明显下调(P<0.05);与大黄素20μmol/L组比较,大黄素20μmol/L组+丙酮酸组对胃癌MGC803细胞的HK2和FOXD1蛋白表达明显上调(P<0.05)。结论:大黄素可能通过糖酵解代谢途径,抑制胃癌细胞致癌基因FOXD1的表达,达到抗肿瘤的作用。Objective:To investigate the possible mechanism of emodin inhibiting the expression of oncogene FOXD1 in gastric cancer cells through the glycolytic metabolism pathway.Methods:Gastric cancer MGC803 cells were intervened by emodin.CCK8,scratch,and Transwell tests were conducted to detect the changes in the biological characteristics of cells,and glucose and lactic acid kits were used to detect the changes in cell metabolism.The expressions of heterophosphatase(HK2),lactate dehydrogenase A(LDHA),and FOXD1 in gastric cancer tissue were analyzed by the Gene Expression Profiling Interactive Analysis(GEPIA)database.The effects of emodin on the expressions of HK2,LDHA,and FOXD1 proteins were detected by Western blot.Pyruvate was added to determine whether the inhibitory effect of emodin could be reversed.Results:Compared with the blank control group,the proliferation,migration,and invasion abilities of gastric cancer MGC803 cells in the emodin group were significantly reduced(P<0.05),and glucose consumption and lactic acid production were significantly reduced(P<0.05).GEPIA database analysis showed that compared with normal gastric tissue,the expressions of HK2,LDHA,and FOXD1 in gastric cancer tissue were significantly up-regulated(P<0.05).Compared with those in the blank control group,the protein expression levels of HK2 and FOXD1 in gastric cancer MGC803 cells in the emodin group were significantly down-regulated(P<0.05).Compared with those in the emodin group,the protein expressions of HK2 and FOXD1 in gastric cancer MGC803 cells in the emodin+pyruvate group were significantly up-regulated(P<0.05).Conclusion:Emodin may inhibit the expression of oncogene FOXD1 in gastric cancer cells through a glycolytic metabolism pathway to achieve the anti-tumor effect.

关 键 词：大黄素 胃癌 糖酵解代谢 叉头框蛋白D1 己糖激酶Ⅱ 乳酸脱氢酶A 

分 类 号：R73[医药卫生—肿瘤]