Metformin inhibits gastric cancer via the inhibition of HIF1α/PKM2 signaling

American Journal of Cancer Research

Volumn 5, Issue 4, 2015, Pages 1423-1434

  Chen, Guangxia ^a,b   Feng, Wan ^c   Zhang, Shu ^c   Bian, Kangqi ^a   Yang, Yan ^d   Fang, Cheng ^a   Chen, Min ^c   Yang, Jun ^c   Zou, Xiaoping ^a,c  

^a THE AFFILIATED DRUM TOWER HOSPITAL OF NANJING UNIVERSITY MEDICAL SCHOOL   (China)

^b First People's Hospital of Xuzhou   (China)

^c MEDICAL SCHOOL OF NANJING UNIVERSITY   (China)

^d XUZHOU CENTRAL HOSPITAL   (China)

Author keywords

Gastric cancer; Hypoxia inducible factor 1 ; Metformin; Pyruvate kinase M2

Indexed keywords

HYPOXIA INDUCIBLE FACTOR 1ALPHA; METFORMIN; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROSTAGLANDIN SYNTHASE; PROTEIN KINASE B; PYRUVATE KINASE; PYRUVATE KINASE M2; UNCLASSIFIED DRUG;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CELL CYCLE ARREST; CELL INVASION; CELL VIABILITY; CONTROLLED STUDY; DRUG MECHANISM; FLOW CYTOMETRY; HUMAN; HUMAN CELL; HUMAN TISSUE; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; MIGRATION INHIBITION; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; STOMACH CANCER; WESTERN BLOTTING;

EID: 85006216347     PISSN: None     EISSN: 21566976     Source Type: Journal    
DOI: None     Document Type: Article

References (26)

1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011; 61: 69-90.
2. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55: 74-108.
3. Macintyre AN, Rathmell JC. Activated lymphocytes as a metabolic model for carcinogenesis. Cancer Metab 2013; 23: 1-5.
4. Kumar A, Kant S, Singh SM. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: a role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation. Toxicol Appl Pharmacol 2013; 273: 196-208.
5. Tavares-Valente D, Baltazar F, Moreira R, Queirós O. Cancer cell bioenergetics and pH regulation influence breast cancer cell resistance to paclitaxel and doxorubicin. J Bioenerg Bio-membr 2013; 45: 467-475.
6. Brauer HA, Makowski L, Hoadley KA, Casbas-Hernandez P, Lang LJ, Romàn-Pèrez E, D'Arcy M, Freemerman AJ, Perou CM, Troester MA. Impact of tumor microenvironment and epithelial phenotypes on metabolism in breast cancer. Clin Cancer Res 2013; 19: 571-585.
7. Carito V, Bonuccelli G, Martinez-Outschoorn UE, Whitaker-Menezes D, Caroleo MC, Cione E, Howell A, Pestell RG, Lisanti MP, Sotgia F. Metabolic remodeling of the tumor microenvironment: migration stimulating factor (MSF) reprograms myofibroblasts toward lactate production, fueling anabolic tumor growth. Cell Cycle 2012; 11: 3403-3414.
8. Kumar V, Gabrilovich DI. Hypoxia inducible factors in regulation of immune responses in tumor microenvironment. Immunology 2014; 143: 512-519.
9. Ohashi T, Akazawa T, Aoki M, Kuze B, Mizuta K, Ito Y, Inoue N. Dichloroacetate improves immune dysfunction caused by tumor-secreted lactic acid and increases antitumor immunoreactivity. Int J Cancer 2013; 133: 1107-1118.
10. Meijer TW, Kaanders JH, Span PN, Bussink J. Targeting hypoxia, HIF-1, and tumor glucose metabolism to improve radiotherapy efficacy. Clin Cancer Res 2012; 18: 5585-5594.
11. Semenza GL. HIF1 mediates metabolic resp- onses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013; 123: 3664-3671.
12. Yu GT, Bu LL, Zhao YY, Liu B, Zhang WF, Zhao YF, Zhang L, Sun ZJ. Inhibition of mTOR reduce Stat3 and PAI related angiogenesis in salivary gland adenoid cystic carcinoma. Am J Cancer Res 2014; 4: 764-775.
13. Liu Z, Jia X, Duan Y, Xiao H, Sundqvist KG, Permert J, Wang F. Excess glucose induces hypoxia-inducible factor-1α in pancreatic cancer cells and stimulates glucose metabolism and cell migration. Cancer Biol Ther 2013; 14: 428-435.
14. McFarland MS, Cripps R. Diabetes mellitus and increased risk of cancer: focus on metformin and the insulin analogs. Pharmacotherapy 2010; 30: 1159-1178.
15. Tseng CH. Metformin reduces thyroid cancer risk in taiwanese patients with type 2 diabetes. PLoS One 2014; 9: e109852.
16. Franciosi M, Lucisano G, Lapice E, Strippoli GF, Pellegrini F, Nicolucci A.Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One 2013; 2: e71583.
17. Goscinski MA, Nesland JM, Giercksky KE, Dhakal HP. Primary tumor vascularity in esophagus cancer-CD34 and HIF1-α expression correlate with tumor progression. Histol His-topathol 2013; 28: 1361-1368.
18. Tong Y, Li QG, Xing TY, Zhang M, Zhang JJ, Xia Q. HIF1 regulates WSB-1 expression to promote hypoxia-induced chemoresistance in hepatocellular carcinoma cells. FEBS Lett 2013; 587: 2530-2535.
19. Liu R, Li Z, Bai S, Zhang H, Tang M, Lei Y, Chen L, Liang S, Zhao YL, Wei Y, Huang C. Mechanism of cancer cell adaptation to metabolic stress: proteomics identification of a novel thyroid hormone-mediated gastric carcinogenic signaling pathway. Mol Cell Proteomics 2009; 8: 70-85.
20. Semenza GL. HIF1: upstream and downstream of cancer metabolism. Curr Opin Genet Dev 2010; 20: 51-56.
21. Kumar A, Kant S, Singh SM. Antitumor and chemosensitizing action of dichloroacetate implicates modulation of tumor microenvironment: a role of reorganized glucose metabolism, cell survival regulation and macrophage differentiation. Toxicol Appl Pharmacol 2013; 273: 196-208.
22. Warburg O. On the origin of cancer cells. Science 1956; 123: 309-314.
23. Chaneton B, Gottlieb E. Rocki ng cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci 2012; 37: 309-316.
24. Martinez-Outschoorn UE, Pestell RG, Howell A, Tykocinski ML, Nagajyothi F, Machado FS, Tanowitz HB, Sotgia F, Lisanti MP. Energy transfer in "parasitic" cancer metabolism: Mito- chondria are the powerhouse and Achilles' heel of tumor cells. Cell Cycle 2011; 10: 4208-4216.
25. Wheaton WW, Weinberg SE, Hamanaka RB, Soberanes S, Sullivan LB, Anso E, Glasauer A, Dufour E, Mutlu GM, Budigner GS, Chandel NS. Metformin inhibits mitochondrial complex I of cancer cells to reduce tumorigenesis. Elife 2014; 3: e02242.
26. Ibrahim MY, Hashim NM, Mohan S, Abdulla MA, Kamalidehghan B, Ghaderian M, Dehghan F, Ali LZ, Arbab IA, Yahayu M, Lian GE, Ahmadipour F, Ali HM. α-Mangostin from Cratoxylum arborescens demonstrates apoptogenesis in MCF-7 with regulation of NF-κB and Hsp70 protein modulation in vitro, and tumor reduction in vivo. Drug Des Devel Ther 2014; 8: 1629-1647.