食品与发酵工业 >

2020 , Vol. 46 >Issue 10: 53 - 59

DOI: https://doi.org/10.13995/j.cnki.11-1802/ts.023474

研究报告

甘露糖通过下调GLUT1抑制结直肠癌发生及增殖

  • 王浩 ,
  • 李海涛
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  • (江南大学 食品学院,江苏 无锡,214122)
硕士研究生(李海涛教授为通讯作者,E-mail:liht@jiangnan.edu.cn)

收稿日期: 2020-01-31

  网络出版日期: 2020-06-17

基金资助

国家自然科学基金资助项目(81773064)

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Mannose inhibits the occurrence and proliferation of colorectal cancer by down-regulating GLUT1

  • WANG Hao ,
  • LI Haitao
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  • (School of Food Science and Technology, Jiangnan University, Wuxi 214122, China)

Received date: 2020-01-31

  Online published: 2020-06-17

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摘要

为探究甘露糖对结直肠肿瘤发生及增殖的影响,并进一步解释作用机制。该文建立原发结直肠肿瘤小鼠模型,发现甘露糖的干预,能够显著降低结直肠肿瘤病灶的发生率以及发展程度;通过细胞实验,发现一定剂量甘露糖可以显著减弱结直肠癌细胞系HCT116及HT29的增殖,且在刺激浓度为25 mmol/L作用48 h后,能够显著降低两者培养液中葡萄糖的消耗量,分别达到(68.40±3.43)%及(58.78±1.27)%;通过蛋白质印迹法,发现甘露糖可降低这2株细胞系中葡萄糖转运载体蛋白GLUT1表达,在动物模型的结直肠组织中也得到了一致的结果。结论显示,甘露糖能够在体外干扰结直肠癌细胞葡萄糖摄取及增殖,降低原发结直肠肿瘤小鼠模型的结直肠肿瘤发生率及发展程度,认为此现象与葡萄糖转运载体蛋白GLUT1表达下调有关。

关键词： 甘露糖; 结直肠肿瘤; 细胞增殖; GLUT1

本文引用格式

王浩 , 李海涛 . 甘露糖通过下调GLUT1抑制结直肠癌发生及增殖[J]. 食品与发酵工业, 2020 , 46(10) : 53 -59 . DOI: 10.13995/j.cnki.11-1802/ts.023474

Abstract

The objective of this study was to evaluate the effect of mannose on colorectal tumorigenesis and proliferation, and explain the mechanism. Establishing a mouse model of primary colorectal tumors showed that daily administration of mannose could significantly attenuate colitis-associated colorectal tumorigenesis in mice. Moreover, mannose also suppressed the growth of colon cancer cells HCT116 and HT29 in cell experiments. With mannose concentration of 25 mmol/L, the glucose comsumption of these two cell lines reduced to (68.40±3.43)% and (58.78±1.27)% after 48 hours, respectively. Western blotting showed that mannose could down-regulate the expression of glucose transporter protein GLUT1 in both cell lines and mice. Taken together, we suggested that mannose could disturb the glucose uptake and suppress the proliferation of colon cancer cells in vitro, and attenuate tumorigenesis in mice, which was related to the down-`regulation of GLUT1.

Key words： mannose; colorectal cancer; cell proliferation; GLUT1

参考文献

[1] EVELIEN D, PIETER J T, JASPER L A V, et al. Colorectal cancer[J]. Lancet, 2019, 394(10 207): 1 467-1 480.
[2] KANG YUN PYO, WARD NATHAN P, DENICOLA GINA M. Recent advances in cancer metabolism: A technological perspective[J]. Experimental & molecular medicine, 2018,50(4): 1-16.
[3] MEESTER REINIER G S, MANNALITHARA A, LANSDORP-VOGELAAR I, et al. Trends in incidence and stage at diagnosis of colorectal cancer in adults aged 40 through 49 years, 1975-2015[J]. JAMA, 2019, 321(19): 1 933-1 934.
[4] MA Y, YANG W S, SIMON TRACEY G, et al. Dietary patterns and risk of hepatocellular carcinoma among U.S. men and women[J]. Hepatology (Baltimore, Md.), 2019, 70(2): 577-586.
[5] CYNTHIA L S, WENDY S G. Microbes, microbiota, and colon cancer[J]. Cell Host & Microbe, 2014, 15(3): 317-328.
[6] AMANDINE V, SELMA M. Circadian clocks and cancer: Timekeeping governs cellular metabolism[J]. Trends in Endocrinology & Metabolism, 2019, 30(7): 445-458.
[7] KATO Y, MAEDA T, SUZUKI A, et al. Cancer metabolism: new insights into classic characteristics[J]. Japanese Dental Science Review, 2018, 54(1): 8-21.
[8] LIN J, XIA L, LIANG J, et al. The roles of glucose metabolic reprogramming in chemo-and radio-resistance[J]. Journal of Experimental & Clinical Cancer Research, 2019, 38(1): 218.
[9] GONCALVES M D, LU C, TUTNAUER J, et al. High-fructose corn syrup enhances intestinal tumor growth in mice[J]. Science, 2019, 363(6 433): 1 345-1 349.
[10] GONZALEZ P S, O’PREY J, CARDACI S, et al. Mannose impairs tumour growth and enhances chemotherapy[J]. Nature, 2018, 563(7 733): 719-723.
[11] DENG D, XU C, SUN P, et al. Crystal structure of the human glucose transporter GLUT1[J]. Nature, 2014, 510(7 503): 121-134.
[12] WANG J, YE C, CHEN C, et al. Glucose transporter GLUT1 expression and clinical outcome in solid tumors: A systematic review and meta-analysis[J]. Oncotarget, 2017, 8(10): 16 875-16 886.
[13] FENG W, CUI G, TANG C W, et al. Role of glucose metabolism related gene GLUT1 in the occurrence and prognosis of colorectal cancer[J]. Oncotarget, 2017, 8(34): 56 850-56 857.
[14] VUKSAN V, JENKINS D J, SPADAFORA P, et al. Konjac-mannan (glucomannan) improves glycemia and other associated risk factors for coronary heart disease in type 2 diabetes:A randomized controlled metabolic trial[J]. Diabetes Care, 1999, 22(6): 913-919.
[15] FRANCESCANGELI F, DE ANGELIS M L, ZEUNER A. Dietary factors in the control of gut homeostasis, intestinal stem cells, and colorectal cancer[J]. Nutrients, 2019, 11(12): 2 936.
[16] ARNOLD M, SIERRA M S, LAVERSANNE M, et al. Global patterns and trends in colorectal cancer incidence and mortality[J]. Gut, 2017, 66(4): 683-691.
[17] DEBERARDINIS R J, SAYED N, DITSWORTH D, et al. Brick by brick: Metabolism and tumor cell growth[J]. Current Opinion In Genetics & Development, 2008, 18(1): 54-61.
[18] VALLéE A, LECARPENTIER Y, GUILLEVIN R, et al.Demyelination in multiple sclerosis: reprogramming energy metabolism and potential PPARγ agonist treatment approaches[J]. International journal of Molecular Sciences, 2018, 19(4): 1 212.
[19] KIM J.Regulation of immune cell functions by metabolic reprogramming[J/OL]. Journal of Immunology Research,DOI:10.1155/2018/8605471.
[20] SU B,SU J, ZENG Y, et al. Diallyl disulfide inhibits TGF-β1-induced upregulation of Rac1 and β-catenin in epithelial-mesenchymal transition and tumor growth of gastric cancer[J]. Oncology Reports, 2018, 39(6): 2 797-2 806.
[21] HAMANAKA R B, CHANDEL N S. Targeting glucose metabolism for cancer therapy[J]. Journal of Experimental Medicine, 2012, 209(2): 211-215.
[22] ZHANG D, CHINA C, JIAO X, et al. D-mannose induces regulatory T cells and suppresses immunopathology[J]. Nature Medicine, 2017, 23(9): 1 036-1 045.
[23] WANG T, NING K, LU T X, et al. Elevated expression of TrpC5 and GLUT1 is associated with chemoresistance in colorectal cancer[J]. Oncology Reports, 2017, 37(2): 1 059-1 065.
[24] NAY H. Reprogramming glucose metabolism in cancer: Can it be exploited for cancer therapy?[J]. Nature Reviews Cancer,2016, 16(10): 635-649.
[25] YAMAMOTO T, SEINO Y, FUKUMOTO H, et al.Over-expression of facilitative glucose transporter genes in human cancer[J]. Biochemical and Biophysical Research Communications, 1990, 170(1): 223-230.
[26] WINCEWICZ A SM, KODA M, et al.Significant coexpression of GLUT-1, Bcl-xL, and bax in colorectal cancer[J]. Annals of the New York Academy of Sciences, 2007, 1 095(1): 53-61.
[27] YOUNES M, LECHAGO L V, SOMOANO J R, et al. Wide expression of the human erythrocyte glucose transporter Glut1 in human cancers[J]. Cancer Res, 1996, 56(5): 1 164-1 167.
[28] ZHAO X J, LU C P, CHU W W, et al.MicroRNA-124 suppresses proliferation and glycolysis in non-small cell lung cancer cells by targeting AKT-GLUT1/HKII[J]. Tumor Biology, 2017, 39(5): 1-9.
[29] ZHANG W, XU Y, XU Q, et al. PPARδ promotes tumor progression via activation of Glut1 and SLC1-A5 transcription[J]. Carcinogenesis, 2017, 38(7): 748-755.
[30] KRAUS D, RECKENBEIL J, WENGHOEFER M, et al. Ghrelin promotes oral tumor cell proliferation by modifying GLUT1 expression[J]. Cellular and Molecular Life Sciences, 2016, 73(6): 1 287-1 299.
[31] DING J, GOU Q, JIN J, et al. Metformin inhibits PPARδ agonist-mediated tumor growth by reducing Glut1 and SLC1A5 expressions of cancer cells[J]. European Journal of Pharmacology, 2019, 857: 172 425.
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