幽门螺杆菌感染对胃癌细胞糖酵解的影响

doi:10.6040/j.issn.1671-7554.0.2022.0965

摘要/Abstract

摘要： 目的探讨幽门螺杆菌(H. pylori)对胃癌细胞糖酵解的影响及分子机制。方法通过检测胃黏膜上皮细胞GES-1与6种胃癌细胞(MKN28、AGS、HGC27、MGC803、MKN45、NCI-N87)的葡萄糖消耗速率和乳酸产量,确定GES-1和两种胃癌细胞MKN28、AGS为后续研究对象。将GES-1、MKN28和AGS细胞分别与H. pylori(H. pylori-HVS、H. pylori-26695、H. pylori-△cagA)共培养,构建H. pylori急性和慢性感染的细胞模型,将未感染H. pylori的3种细胞设置为对照组。在所有细胞模型中检测葡萄糖消耗、乳酸生成和葡萄糖摄取,并且通过Western blotting检测糖酵解关键酶的蛋白表达水平。结果与正常胃黏膜上皮细胞GES-1比较,多种胃癌细胞(AGS、HGC27、MGC803、MKN45、NCI-N87)中葡萄糖消耗和乳酸生成上调,差异均有统计学意义(P均<0.001)。与未感染H. pylori的对照组细胞比较,H. pylori急性感染不影响GES-1和两种胃癌细胞MKN28、AGS的葡萄糖摄取和乳酸生成,差异均无统计学意义(P均>0.05);而H. pylori慢性感染导致GES-1和两种胃癌细胞MKN28、AGS的葡萄糖摄取和乳酸生成增加,差异均有统计学意义(P均<0.001)。Western blotting结果显示,在H. pylori慢性感染的胃癌细胞中,PKM2(丙酮酸激酶M2亚型)表达水平上调,而PKM1(丙酮酸激酶M1亚型)表达水平下调。结论 H. pylori慢性感染可上调胃癌细胞的糖酵解,其分子机制可能与PKM2有关,提示PKM2可能是H. pylori介导胃癌代谢改变的靶点。

关键词: 幽门螺杆菌, 丙酮酸激酶, 胃癌, 代谢, 糖酵解

Abstract: Objective To explore the effects of Helicobacter pylori(H. pylori)on glycolysis metabolism of gastric cancer cells and the molecular mechanism. Methods After the glucose consumption rate and lactate production of gastric mucosal epithelial cells GES-1 and gastric cancer cells including MKN28, AGS, HGC27, MGC803, MKN45 and NCI-N87 were detected, GES-1, MKN28 and AGS were identified as the follow-up research objects. Untreated GES-1, MKN28 and AGS were set as controls, while they were co-cultured with H. pylori(H. pylori-HVS, H. pylori-26695, H. pylori-△cagA)to establish acute and chronic cell models. Glucose consumption, lactate production and glucose uptake were measured in all cell models. The protein levels of key enzymes in glucose metabolism were detected with Western blotting. Results Compared with normal gastric mucosal GES-1 cells, the gastric cancer cells(AGS, HGC27, MGC803, MKN45, NCI-N87)had significantly up-regulated glycolysis(P<0.001). Compared with the controls, the acute models had unchanged glucose uptake and lactate production(P>0.05), while chronic models had significantly increased glucose uptake and lactate production(P<0.001). The expression level of M2 isoform of pyruvate kinase(PKM2)was significantly up-regulated in the acute models, while that of M1 isoform of pyruvate kinase(PKM1)was down-regulated. Conclusion Chronic H. pylori infection can up-regulate glycolysis in gastric cancer cells, and the molecular mechanism may be related to PKM2, suggesting that PKM2 may be the target of H. pylori-mediated metabolic changes in gastric cancer.

Key words: Helicobacter pylori, Pyruvate kinase, Gastric cancer, Metabolism, Glycolysis

中图分类号:

R735.2

王赞,徐晓涵,张瑜,曲业敏,王明义,陈艾. 幽门螺杆菌感染对胃癌细胞糖酵解的影响[J]. 山东大学学报 (医学版), 2023, 61(2): 16-24.

WANG Zan, XU Xiaohan, ZHANG Yu, QU Yemin, WANG Mingyi, CHEN Ai. Effects of Helicobacter pylori infection on glycolysis of gastric cancer cells[J]. Journal of Shandong University (Health Sciences), 2023, 61(2): 16-24.

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