Journal of Shandong University (Health Sciences) ›› 2023, Vol. 61 ›› Issue (2): 16-24.doi: 10.6040/j.issn.1671-7554.0.2022.0965

• 基础医学 • Previous Articles     Next Articles

Effects of Helicobacter pylori infection on glycolysis of gastric cancer cells

WANG Zan1,2, XU Xiaohan1, ZHANG Yu3, QU Yemin2, WANG Mingyi2, CHEN Ai1,2   

  1. 1. School of Medical Laboratory, Weifang Medical University, Weifang 261053, Shandong, China;
    2. Department of Central Lab, Weihai Municipal Hospital, Weihai 264200, Shandong, China;
    3. School of Laboratory Medicine, Dalian Medical University, Dalian 116000, Liaoning, China
  • Published:2023-02-17

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

CLC Number: 

  • R735.2
[1] Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries [J]. CA Cancer J Clin, 2021, 71(3): 209-249.
[2] Crowe SE. Helicobacter pylori Infection [J]. N Engl J Med, 2019, 380(12): 1158-1165.
[3] Tshibangu-Kabamba E, Yamaoka Y. Helicobacter pylori infection and antibiotic resistance—from biology to clinical implications [J]. Nat Rev Gastroenterol Hepatol, 2021, 18(9): 613-629.
[4] Keilberg D, Steele N, Fan S, et al. Gastric metabolomics detects helicobacter pylori correlated loss of numerous metabolites in both the corpus and antrum [J]. Infect Immun, 2021, 89(2): e00690-20. doi: 10.1128/IAI.00690-20.
[5] Matsunaga S, Nishiumi S, Tagawa R, et al. Alterations in metabolic pathways in gastric epithelial cells infected with Helicobacter pylori [J]. Microb Pathog, 2018, 124: 122-129. E00690-20. doi: 10.1016/j.micpath.2018.08.033.
[6] Maeda T, Zai H, Fukui Y, et al. Impact of Helicobacter pylori infection on fluid duodenal microbial community structure and microbial metabolic pathways [J]. BMC Microbiol, 2022, 22(1): 27. doi: 10.1186/s12866-022-02437-w.
[7] Reinfeld BI, Rathmell WK, Kim TK, et al. The therapeutic implications of immunosuppressive tumor aerobic glycolysis [J]. Cell Mol Immunol, 2022, 19(1): 46-58.
[8] Bar-Even A, Flamholz A, Noor E, et al. Rethinking glycolysis: on the biochemical logic of metabolic pathways [J]. Nat Chem Biol, 2012, 8(6): 509-517.
[9] Park JH, Pyun WY, Park HW. Cancer metabolism: phenotype, signaling and therapeutic targets[J]. Cells, 2020, 9(10): 2308. doi: 10.3390/cells9102308.
[10] Kao YS, Chen CW, Wei JC. Helicobacter pylori infection and risk of gastric cancer [J]. Lancet Public Health, 2022, 7(4): e302. doi: 10.1016/S2468-2667(22)00041-X.
[11] Ganapathy-Kanniappan S, Geschwind JF. Tumor glycolysis as a target for cancer therapy: progress and prospects [J]. Mol Cancer, 2013, 12: 152. doi: 10.1186/1476-4598-12-152.
[12] Hay N. Reprogramming glucose metabolism in cancer: can it be exploited for cancer therapy? [J]. Nat Rev Cancer, 2016, 16(10): 635-649.
[13] Terebiznik MR, Vazquez CL, Torbicki K, et al. Helicobacter pylori VacA toxin promotes bacterial intracellular survival in gastric epithelial cells [J]. Infect Immun, 2006, 74(12): 6599-6614.
[14] Wang C, Jiang J, Ji J, et al. PKM2 promotes cell migration and inhibits autophagy by mediating PI3K/AKT activation and contributes to the malignant development of gastric cancer [J]. Sci Rep, 2017, 7(1): 2886. doi: 10.1038/s41598-017-03031-1.
[15] Dai T, Zhang X, Zhou X, et al. Long non-coding RNA VAL facilitates PKM2 enzymatic activity to promote glycolysis and malignancy of gastric cancer [J]. Clin Transl Med, 2022, 12(10): e1088. doi: 10.1002/ctm2.1088.
[16] Wu J, Hu L, Chen M, et al. Pyruvate kinase M2 overexpression and poor prognosis in solid tumors of digestive system: evidence from 16 cohort studies [J]. Onco Targets Ther, 2016, 9: 4277-4288. doi: 10.2147/OTT.S106508.
[17] Gui DY, Lewis CA, Vander Heiden MG. Allosteric regulation of PKM2 allows cellular adaptation to different physiological states [J]. Sci Signal, 2013, 6(263): pe7. doi:10.1126/scisignal.2003925.
[18] Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells [J]. Int J Biochem Cell Biol, 2011, 43(7): 969-980.
[19] Zhu S, Guo Y, Zhang X, et al. Pyruvate kinase M2(PKM2)in cancer and cancer therapeutics [J]. Cancer Lett, 2021, 503: 240-248. doi: 10.1016/j.canlet.2020.11.018.
[20] Lee YB, Min JK, Kim JG, et al. Multiple functions of pyruvate kinase M2 in various cell types [J]. J Cell Physiol, 2022, 237(1): 128-148.
[21] Alquraishi M, Puckett DL, Alani DS, et al. Pyruvate kinase M2: a simple molecule with complex functions [J]. Free Radic Biol Med, 2019, 143: 176-192. doi: 10.1016/j.freeradbiomed.2019.08.007.
[22] Dong G, Mao Q, Xia W, et al. PKM2 and cancer: the function of PKM2 beyond glycolysis [J]. Oncol Lett, 2016, 11(3): 1980-1986.
[23] Ryu H, Walker JK, Kim S, et al. Regulation of M2-type pyruvate kinase mediated by the high-affinity IgE receptors is required for mast cell degranulation [J]. Br J Pharmacol, 2008, 154(5): 1035-1046.
[24] Zhang Z, Liu Q, Che Y, et al. Antigen presentation by dendritic cells in tumors is disrupted by altered metabolism that involves pyruvate kinase M2 and its interaction with SOCS3 [J]. Cancer Res, 2010, 70(1): 89-98.
[25] Shimada N, Shinagawa T, Ishii S. Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein [J]. Genes Cells, 2008, 13(3): 245-254.
[26] Duan HF, Hu XW, Chen JL, et al. Antitumor activities of TEM8-Fc: an engineered antibody-like molecule targeting tumor endothelial marker 8 [J]. J Natl Cancer Inst, 2007, 99(20): 1551-1555.
[27] Wu X, Zhou Y, Zhang K, et al. Isoform-specific interaction of pyruvate kinase with hepatitis C virus NS5B [J]. FEBS Lett, 2008, 582(15): 2155-2160.
[28] Mazurek S, Zwerschke W, Jansen-Durr P, et al. Effects of the human papilloma virus HPV-16 E7 oncoprotein on glycolysis and glutaminolysis: role of pyruvate kinase type M2 and the glycolytic-enzyme complex [J]. Biochem J, 2001, 356(Pt 1): 247-256.
[29] Gupta V, Bamezai RN. Human pyruvate kinase M2: a multifunctional protein[J]. Protein Sci, 2010, 19(11): 2031-2044.
[30] 孟雨,李燕京,白玉贤. M2型丙酮酸激酶非代谢功能在肿瘤治疗中的研究进展[J]. 现代肿瘤医学, 2022, 30(17): 3230-3234. MENG Yu, LI Yanjing, BAI Yuxian. Research progress of non-metabolic function of M2 pyruvate kinase in cancer treatment [J]. Journal of Modern Oncology, 2022, 30(17): 3230-3234.
[31] Shiroki T, Yokoyama M, Tanuma N, et al. Enhanced expression of the M2 isoform of pyruvate kinase is involved in gastric cancer development by regulating cancer-specific metabolism [J]. Cancer Sci, 2017, 108(5): 931-940.
[32] Dong T, Yan Y, Chai H, et al. Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture [J]. Biomed Pharmacother, 2015, 69: 277-284.
[33] Dai T, Zhang X, Zhou X, et al. Long non-coding RNA VAL facilitates PKM2 enzymatic activity to promote glycolysis and malignancy of gastric cancer [J]. Clin Transl Med, 2022, 12(10): e1088. doi: 10.1002/ctm2.1088.
[1] FU Jia, WANG Lulu, HU Shuai, CHEN Zheping, LIU Dongyi, LI Qingsong, LU Guodong, ZHANG He, ZHAO Xin, FENG Chang. Effects of different approaches of quadrates lumborum block on postoperative recovery of patients undergoing radical gastrectomy [J]. Journal of Shandong University (Health Sciences), 2022, 60(8): 50-57.
[2] BAO Shuqing, YANG Mingyue, LIU Duanrui, WANG Yunshan, JIA Yanfei. Role of NOX4 in ROS induction by Helicobacter pylori in gastric cancer cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(6): 19-25.
[3] WANG Jing, XIE Yan, LI Peilong, DU Lutao, WANG Chuanxin. Value of abnormal methylation of cg16212145 on GZMB gene in early screening of gastric cancer [J]. Journal of Shandong University (Health Sciences), 2022, 60(6): 26-34.
[4] GAO Huiru, DU Tiantian, WANG Yunshan, DU Lutao, WANG Chuanxin. Characterization of regulatory T cells in gastric cancer based on single-cell RNA sequencing data [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 43-49.
[5] LYU Yanhong, ZHANG Zhimian. Correlation of helicobacter pylori infection and hypertension in the 2,809 physical examination participants [J]. Journal of Shandong University (Health Sciences), 2022, 60(2): 43-47.
[6] MU Yanxi, WANG Wenjie, CHEN Kang, YAO Yalong, LI Jinzhou, WEI Haoqi, LIU Haipeng, HUANG Zeping, CHEN Xiao. Exploring the clinicopathological features of three cases of gastric cancer in one pedigree during short-term [J]. Journal of Shandong University (Health Sciences), 2022, 60(11): 96-101.
[7] CHU Yan, LIU Duanrui, ZHU Wenshuai, FAN Rong, MA Xiaoli, WANG Yunshan, JIA Yanfei. Expressions of DNA methyltransferases in gastric cancer and their clinical significance [J]. Journal of Shandong University (Health Sciences), 2021, 59(7): 1-9.
[8] HU Yanwen, WANG Zhiyuan, YU Wanjiang, ZHAO Huichen, HAN Heli, XU Zhipeng, MA Hong, ZHANG Yuchao, LIU Yuantao. Correlation of fat distribution with metabolic syndrome and glucose metabolism in 52 obese patients [J]. Journal of Shandong University (Health Sciences), 2020, 1(8): 101-106.
[9] SHI Shuang, LI Juan, MI Qi, WANG Yunshan, DU Lutao, WANG Chuanxin. Construction and application of a miRNAs prognostic risk assessment model of gastric cancer [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 47-52.
[10] LI Yan, SUN Fengjiao, ZHANG Tianran, WANG Yuxin, ZHANG Zhengduo, GAO Xibao. Effects of high-sugar, high-fat diet and different concentrations of selenium on lipid metabolism and oxidative stress in rats [J]. Journal of Shandong University (Health Sciences), 2020, 58(5): 98-106.
[11] SUN Fengjiao, LI Yan, WANG Yuxin, ZHANG Tianran, WU Hong, GAO Xibao. Effects of dietary structure and selenium concentration on glucose metabolism in rats [J]. Journal of Shandong University (Health Sciences), 2020, 58(2): 36-43.
[12] LIU Yuanyuan, WANG Pei, CHU Haichen. Effects of different anesthesia depths on the cerebral oxygen metabolism indexes in 150 patients undergoing brain surgery [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 65-71.
[13] ZHI Mengwei, JIANG Zhiwei, DAI Xinjuan, WANG Gang, CHENG Wei. Clinical observation of heart rate variability in patients with gastric cancer during perioperative period under the guidance of enhanced recovery after surgery [J]. Journal of Shandong University (Health Sciences), 2020, 58(11): 85-91.
[14] WANG Yajie, WEN Bei, SHI Haoyu, SHANG Liang, DONG Kangdi, LI Leping. Gastric cancer complicated with mild hemophilia and postoperative hemorrhage: a report of one case [J]. Journal of Shandong University (Health Sciences), 2020, 58(1): 91-93.
[15] LI Leping, CUI Huaiping, SHANG Liang. Application of enhanced recovery after surgery in gastrointestinal surgery [J]. Journal of Shandong University (Health Sciences), 2019, 57(9): 5-11.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!