摘要
背景:已有研究发现质子泵抑制剂(PPI)可抑制空泡型质子泵(V-ATPases)表达、影响胃癌细胞糖酵解水平。V-ATPases对肿瘤恶性生物学行为具有重要意义。目的:探讨PPI通过抑制糖酵解和谷氨酰胺代谢作用于胃癌的机制。方法:在细胞实验部分,对胃癌细胞株进行PPI加药处理并沉默相关分子,以CCK-8法检测细胞增殖,流式细胞术检测细胞凋亡,定量PCR和蛋白质印迹法分别检测mRNA和蛋白表达。在动物实验部分,将裸鼠分为空白对照组、0.9%NaCl溶液灌胃组、泮托拉唑钠溶液灌胃组、PKM2干扰组,观察小鼠体质量、摄食行为、肿瘤大小以及肿瘤组织内相关通路分子表达情况。结果:PPI可抑制胃癌细胞增殖,诱导细胞凋亡;PPI可抑制胃癌细胞糖酵解和谷氨酰胺代谢相关分子表达;干扰PKM2或PI3K均可抑制胃癌细胞增殖,诱导细胞凋亡;沉默V-ATPases可抑制胃癌细胞糖酵解和谷氨酰胺代谢相关分子表达。PPI灌胃治疗荷瘤小鼠可延缓肿瘤生长、缓解小鼠恶病质情况。结论:PPI可抑制V-ATPases和PI3K信号通路表达,进而影响胃癌细胞糖酵解和谷氨酰胺代谢水平,影响胃癌细胞增殖和凋亡水平,从而发挥抗肿瘤作用。
Background:Studies have showed that proton pump inhibitor(PPI)can inhibit the expression of V-ATPases and influence the glycolysis of gastric cancer cells.V-ATPases have important significance on malignant biological behavior of tumor.Aims:To explore the mechanisms of PPI on gastric cancer via inhibiting glycolysis and glutamine metabolism.Methods:In the cell experiment,gastric cancer cell lines were cultured with PPI and knockdown of related molecules,cell proliferation was determined by CCK-8 assay,cell apoptosis was detected by flow cytometry.mRNA and protein expressions of related molecules were detected by quantitative PCR and Western blotting,respectively.In the animal experiment,nude mice were divided into blank control group,0.9%NaCl solution group,pantoprazole sodium group,and PKM2 group,body weight,feeding behavior,tumor size and expressions of related pathway molecule in tumor tissue were compared.Results:PPI could inhibit the proliferation and induce apoptosis of gastric cancer cells.PPI could suppress the expression of related molecules of glycolysis and glutamine metabolism.Knocking down PKM2 or PI3K could inhibit proliferation and induce apoptosis of gastric cancer cells.Silencing V-ATPases inhibited the expression of related molecules of glycolysis and glutamine metabolism in gastric cancer cells.PPI therapy delayed tumor growth and reduced cachexia in tumor-bearing mice.Conclusions:PPI may inhibit cell proliferation and induce cell apoptosis by influencing glycolysis and glutamine metabolism of gastric cancer cells via suppressing V-ATPases and PI3K pathway,thus to play an anti-tumor role.
作者
王卓婷
邹晓平
陈敏
沈永华
黄淑玲
顾正宇
WANG Zhuoting;ZOU Xiaoping;CHEN Min;SHEN Yonghua;HUANG Shuling;GU Zhengyu(Department of Gastroenterology, Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, Nanjing ,210008)
出处
《胃肠病学》
2020年第3期136-144,共9页
Chinese Journal of Gastroenterology
基金
南京市卫生科技发展专项资金项目(YKK18088)。
作者简介
共同通信作者:邹晓平,Email:13770771661@163.com;共同通信作者:陈敏,Email:croweminchan@aliyun.com。
