摘要
“Warburg效应”是肿瘤细胞重要的代谢特征之一，肿瘤细胞在氧气充足的条件下仍进行糖酵解，亦称“有氧糖酵解”。愈来愈多的研究表明肿瘤是一种代谢性疾病。因此探索肿瘤代谢变化及机制，以及靶向肿瘤代谢的肿瘤治疗成为近年来肿瘤研究的热点。目前基于肿瘤代谢的一些治疗方法（如生酮疗法、大剂量维生素C等）逐步引起基础研究和临床研究工作者的重视。最近有研究报导，甘露糖可以抑制肿瘤生长、增加阿霉素抗癌效果和延长荷瘤小鼠生存期。其主要作用机制是干扰葡萄糖代谢、促进肿瘤细胞凋亡以及增强化疗药物顺铂和阿霉素的抗肿瘤作用。此外，甘露糖还有调节免疫平衡等作用。甘露糖作为一种营养素，对人体健康无害，有望成为一种重要肿瘤代谢调节治疗的营养素，并且可与一线肿瘤治疗（化疗和放疗）配合来提高抗肿瘤治疗效果，具有重要的临床意义和应用前景。
Abstract
“Warburg effect” is one of the important metabolic characteristics of tumor cells. Tumor cells still undergo glycolysis under the condition of sufficient oxygen， which is also known as “aerobic glycolysis”. Many studies have shown that cancer is a metabolic disease. Therefore， to explore the changes and mechanisms of tumor metabolism， as well as tumor metabolic regulation therapy targeting tumor metabolism， have become a focus of tumor research in recent years. At present， some treatment methods based on tumor metabolism， such as ketogenic therapy and high-dose vitamin C， have gradually attracted the attention of basic research and clinical research. Recently， it has been reported that mannose can inhibit tumor growth， increase the anti-cancer effect of adriamycin and prolong the survival period of tumor-bearing mice. It mainly interferes with glucose metabolism and enhances the anti-tumor effect of chemotherapy drugs cisplatin and adriamycin to promote tumor cell apoptosis. In addition， mannose still has the effect of regulating immunity balance. Mannose， as a nutrient， is harmless to human health， and is expected to become an important nutrient for tumor metabolism regulation therapy， and can be combined with first-line tumor therapy (chemotherapy and radiotherapy) to improve the anti-tumor treatment effect， which has important clinical significance and application prospect.
关键词
甘露糖 /
Warburg效应 /
肿瘤代谢 /
抗肿瘤
Key words
Mannose /
Warburg effect /
Tumor metabolism /
Anti-tumor
1，4宋蒙蒙，2陈哲文，3李晔，1，4宋春花，5石汉平，6缪明永.
甘露糖抗肿瘤作用的研究进展[J]. 肿瘤代谢与营养电子杂志. 2019, 6(3): 283-286 https://doi.org/10.16689/j.cnki.cn11-9349/r.2019.03.003
1，4 SONG Meng-meng，2CHEN Zhe-wen，3 LI Ye，1，4 SONG Chun-hua，5SHI Han-ping，6MIAO Ming-yong.
Advances in anti-tumor effect of mannose[J]. Electronic Journal of Metabolism and Nutrition of Cancer. 2019, 6(3): 283-286 https://doi.org/10.16689/j.cnki.cn11-9349/r.2019.03.003
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参考文献
1.Koppenol W， Bounds P， Dang C， et al. Otto Warburg’s contributions to current concepts of cancer metabolism. Nat Rev Cancer. 2011;11(5):325-337.
2.Yoshida G. Metabolic reprogramming: the emerging concept and associated therapeutic strategies. J Exp Clin Cancer Res. 2015;34:111.
3.Yun J， Mullarky E， Lu C， et al. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH. Science. 2015;350(6266):1391-1396.
4.Smyl C. Ketogenic diet and cancer-a perspective. Recent Results Cancer Res. 2016;207: 233-240.
5.Gonzalez PS， O’Prey J， Cardaci S， et al. Mannose impairs tumour growth and enhances chemotherapy. Nature. 2018;563(7733):719-723.
6.Thorens B， Mueckler M. Glucose transporters in the 21st century. Am J Physiol Endocrinol Metab. 2010;298(2):E141-E145.
7.DeRossi C， Bode L， Eklund EA， et al. Ablation of mouse phosphomannose isomerase (Mpi) causes mannose 6-phosphate accumulation， toxicity， and embryonic lethality. J Biol Chem. 2006;281(9):5916-5927.
8.李其响，张配，刘浩. 肿瘤细胞能量代谢特点及其研究进展. 中国药理学通报. 2017;33(11):1499-1502.
9.王润泽，李伟民，李建华，等. 肿瘤能量代谢的研究进展. 2017;35(21):345-347.
10.Kianercy A， Veltri R， Pienta KJ. Critical transitions in a game theoretic model of tumour metabolism. Interface Focus. 2014;4(4):20140014.
11.Davis JA， Freeze HH. Studies of mannose metabolism and effects of long-term mannose ingestion in the mouse. Biochim Biophys Acta. 2001;1528(2-3):116-126.
12.Westphal V， Kjaergaard S， Davis JA， et al. Genetic and metabolic analysis of the first adult with congenital disorder of glycosylation type Ib: long-term outcome and effects of mannose supplementation. Mol Genet Metab. 2001;73(1):77-85.
13.Kranjcec B， Papes D， Altarac S. D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol. 2014;32(1):79-84.
14.Hanahan D， Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646-674.
15.Chen XS， Li LY， Guan YD， et al. Anticancer strategies based on the metabolic profile of tumor cells: therapeutic targeting of the Warburg effect. Acta Pharmacol Sin. 2016;37(8):1013-1019.
16.Deng D， Xu C， Sun P， et al. Crystal structure of the human glucose transporter GLUT1. Nature. 2014;510(7503):121-125.
17.Zhang M， Zhuo X， Wang J， et al. Phosphomannose isomerase affects the key enzymes of glycolysis and sucrose metabolism in transgenic sugarcane overexpressing the manA gene. Mol Breed. 2015;35(3):100.
18.Shtraizent N， DeRossi C， Nayar S， et al. MPI depletion enhances O-GlcNAcylation of p53 and suppresses the Warburg effect. Elife. 2017;6.pii: e22477.doi:10.7554/eLife.22477.
19.Reina-Campos M， Moscat J， Diaz-Meco M. Metabolism shapes the tumor microenvironment. Curr Opin Cell Biol. 2017;48:47-53.
20.Wojtkowiak JW， Verduzco D， Schramm KJ， et al. Drug resistance and cellular adaptation to tumor acidic pH microenvironment. Mol Pharm. 2011;8(6):2032-2038.
21.孙林冲，高平. 代谢重编程在调控肿瘤免疫微环境中的作用.生物化学与生物物理进展. 2017;44(8):688-696.
22.Zhang D， Chia C， Jiao X， et al. D-mannose induces regulatory T cells and suppresses immunopathology. Nat Med. 2017;23(9):1036-1045.
基金
国家自然科学基金（81570569）；国家自然科学基金（81672888）
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