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2016, Número 3

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Rev Cuba Endoc 2016; 27 (3)


La metformina como una alternativa en la prevención y tratamiento del cáncer

Licea PME, Hernández RJ

Idioma: Español
Referencias bibliográficas: 62
Paginas: 69-79
Archivo PDF: 165.23 Kb.


RESUMEN

Antecedentes: la metformina, fármaco económico y seguro, ha demostrado mejorar el pronóstico de varios tipos de cánceres.
Objetivo: revisar los aspectos más relevantes de la relación entre la diabetes mellitus, la metformina y el cáncer.
Desarrollo: la diabetes mellitus, en especial la tipo 2, se relaciona con algunos cánceres (mama, hígado, páncreas, ginecológico, vejiga, colon y recto), y en el sexo masculino, aumenta su recurrencia y la mortalidad. Los mecanismos responsables de esta relación no están del todo esclarecidos. La insulina y el factor de crecimiento similar a la insulina en un estado de hiperinsulinismo e insulinorresistencia, pudieran desempeñar un papel fundamental en el desarrollo de cáncer, así como otros factores de riesgo comunes a la diabetes mellitus y al cáncer (alimentación no saludable, sedentarismo, adicciones, edad, sexo, etnia y raza). La proteína liver kinase B1 se ha identificado como una proteína supresora tumoral, y al unirse con la metformina interrumpe el complejo 1 de la cadena respiratoria mitocondrial, y conduce a la disminución de la síntesis de trifosfato de adenosin, y al aumento del cociente proteína activada por mitógenos-trifosfato de adenosin en el espacio intracelular. Los quimioterápicos, esteroides y antiandrógenos, pueden afectar negativamente el metabolismo hidrocarbonado. Algunas drogas antihiperglucemiantes se han relacionado a cánceres específicos, aunque las evidencias son pobres, indirectas y controversiales.
Conclusiones: la metformina pudiera utilizarse en la prevención y el tratamiento de algunos cánceres, y reducir su recurrencia y la mortalidad. Parece existir una relación entre cáncer y la diabetes mellitus, aunque muchos aspectos quedan por dilucidar, como el papel desempeñado por los fármacos anticancerígenos y antihiperglucemiantes utilizados en ambas entidades.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Luo Z, Saha AK, Xiang X, Ruderman NB. AMPK the metabolic syndrome and cancer. Trends Pharmacol Sc. 2005;26:69-76.

  2. Vargas-Hernández VM, Vargas-Aguilar VM, Moreno AD, Acosta G, Kathy Flores K, Tovar LM. Resistencia a la insulina, síndrome metabólico, diabetes mellitus y carcinogénesis mamaria. Rev Hosp Jua Mex. 2014;81:37-49.

  3. González A. Diabetes y cáncer. En: Vargas-Hernández VM. Cáncer en la Mujer. México: Ed. Alfil; 2011. p. 857-62.

  4. Gárciga F, Licea M. Relación entre la diabetes mellitus y el cáncer. Rev Peruana Epidemiol. 2012;16:69-75.

  5. Renehan AG. Diabetes treatment and cancer risk. Diabetes Voice. 2010;55:38-40.

  6. Bowker SL, Majumdar SR, Veugelers P, Johnson JA. Increases cancer-related mortality for patients with type 2 diabetes who use sulfonylurea or insulin. Diabetes Care. 2006;29:254-8.

  7. Monami M, Lamanna C, Balzi D, Marchionni N, Mannucci E. Sulphonylureas and cancer: a case-control study. Acta Diabetol. 2009;46:279-84.

  8. Jonasson JM, Ljung R, Talbäck M, Haglund B, Gudbjörnsdòttir S, Steineck G. Insulin glargine use and short-term incidence of malignancies-a population-based follow-up study in Sweden. Diabetologia. 2009;52:1745-54.

  9. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766-77.

  10. Maiti B, Kundranda MN, Spiro TP, Daw HA. The association of metabolic syndrome with triple-negative breast cancer. Breast Cancer Res Treat. 2010;121:479-83.

  11. Hernández J, Licea ME, Castelo L. Medicamentos que favorecen la pérdida de peso y el control metabólico en las personas obesas con diabetes mellitus tipo 2. Rev Cubana Endocrinol. 2013;24:323-31.

  12. Landman GW, Kleefstra N, Van Hateren KJ, Gronier KH, Gans RO, Bilo HJ. Metformin associated with lower cancer mortality in type 2 diabetes: ZODIAC-16. Diabetes Care. 2010;33:322-6.

  13. Castro MG, Castillo V, Ochoa A, Godínez SA. La metformina y sus aplicaciones actuales en la clínica. Med Int Mex. 2014;30:562-74.

  14. Evans JMM, Donnelly LA, Emslie-Smith AM, Alessi DR, Morris AD. Metformin and reduced risk of cancer in diabetic patients. Br Med J. 2005;330:1304-5.

  15. Sun G, Kashyap SR. Cancer risk in type 2 diabetes mellitus: metabolic links and therapeutic considerations. J Nutr Metab. 2011;(8):270-81.

  16. Dowling RJ, Zakikhani M, Fantus IG, Pollak M, Soonenberg M. Metformin inhibits mammalian target of rapamycin dependent translation initiation in breast cancer cells. Cancer Res. 2007;67:10804-12.

  17. Tosca L, Solnais P, Ferre P, Foufelle F, Dupont J. Metformin induced stimulation of adenosine 5-monophosphate-activated protein kinase (PRKA) impairs progesterone secretion in rat granulose cells. Biol Reprod. 2006;75:342-51.

  18. Teixeira SF, Guimaraes IS, Madeira KP, Daltó RD, Silva IV, Rangel LBA. Metformina sinérgicamente potencializa os efeitos anti proliferativos de cisplastina e etopoisídeo em linhem pulmão NC-H 460. J Bras Pneumol. 2013;39:644-9.

  19. Snima S, Pratheshas P, Cheriam M, Nair AV, Vinoth L. Anti-diabetic drug metformin: Challenges and perspective for cancer therapy. Curr Cancer Drug Target. 2014;14:727-8.

  20. Weinstein D, Simon M, Yehezkel E, Laron Z, Werner H. Insulin analogues display IGF-1-like mitogenic and anti-apoptotic activities in culture cancer cells. Diabetes Metab Res Rev. 2009;25:41-9.

  21. Holly JMP, Perks CM. Cancer as an endocrine problem. Brest Pract Res Clin Endocrinol Metab. 2008;22:539-50.

  22. Boyd DB. Insulin and cancer. Integr Cancer Ther. 2003;2:315-29.

  23. Shiratsuchi I, Akagi Y, Kawahara A, Kinugasa T, Romeo K, Yoshida T, et al. Expression of IGF-1 and IGF-1R and their relation to clinic pathological factors in colorectal cancer. Anticancer Res. 2011;31:2541-5.

  24. Smith U, Gale EA. Does diabetes therapy influence the risk of cancer? Diabetologia. 2009;52:1699-708.

  25. Mardilovich K, Pankratz SHL, Shaw LM. Expression and function of the insulin receptor substrate proteins in cancer. Cell Communication Signaling. 2009;7:14-8.

  26. Bergmann U, Funatomi H, Kornmann M, Beger HG, Korc M. Increased expression of insulin receptor substrate-1 in human pancreatic cancer. Biochem Biophys Res Commun. 1996;220:886-90.

  27. Kornmann M, Maruyama H, Bergmann U, Tangvoranuntakul P, Beger HG, White MF, et al. Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Res. 1998;58:4250-4.

  28. Hellawell GO, Turner GD, Davies DR, Poulsom R, Brewster SF, Macaulay VM. Expression of the type 1 insulin-like growth factor receptor is up-regulated in primary prostate cancer and commonly persists in metastatic disease. Cancer Res. 2002;62:2942-50.

  29. Hoang CD, Zhang X, Scott PD, Guillaume TJ, Maddaus MA, Yee D, et al. Selective activation of insulin receptor substrate-1 and-2 in pleural mesothelioma cells: association with distinct malignant phenotypes. Cancer Res. 2004;64:7479-85.

  30. Boissan M, Beurel E, Wendum D, Rey C, Lecluse Y, Housset C, et al. Over expression of insulin receptor substrate-2 in human and murine hepatocellular carcinoma. Am J Pathol. 2005;167:869-77.

  31. Cantarini MC, de la Monte SM, Pang M, Tong M, D'Errico A, Trevisani F, et al. Aspartyl-asparagyl beta hydroxylase over-expression in human hepatoma is linked to activation of insulin-like growth factor and notch signaling mechanisms. Hepatology. 2006;44:446-57.

  32. Szabolcs M, Keniry M, Simpson L, Reid LJ, Koujak S, Schiff SC, et al. Irs2 inactivation suppresses tumor progression in Pten +/- mice. Am J Pathol. 2009;174:276-86.

  33. Koda M, Sulkowska M, Kanczuga-Koda L, Sulkowski S. Expression of insulin receptor substrate 1 in primary breast cancer and lymph node metastases. J Clin Pathol. 2005;58:645-9.

  34. Ravikumar S, Pérez-Liz G, Del Vale L, Soprano DR, Soprano KJ. Insulin receptor substrate-1 is an important mediator of ovarian cancer cell growth suppression by all-trans retinoic acid. Cancer Res. 2007;67:9266-75.

  35. Han CH, Cho JY, Moon JT, Kim HJ, Kim SK, Shin DH, et al. Clinical significance of insulin receptor substrate-I down-regulation in non-small cell lung cancer. Oncol Rep. 2006;16:1205-10.

  36. Schnarr B, Strunz K, Ohsam J, Benner A, Wacker J, Mayer D. Down-regulation of insulin-like growth factor-I receptor and insulin receptor substrate-1 expression in advanced human breast cancer. Int J Cancer. 2000;89:506-13.

  37. Sisci D, Morelli C, Garofalo C, Romeo F, Morabito L, Casaburi F, et al. Expression of nuclear insulin receptor substrate 1 (IRS-1) in breast cancer. J Clin Pathol. 2006;60:633-41.

  38. Rizos CV, Elisaf MS. Metformin and cancer. Eur J Pharmacol. 2013;705:96-108.

  39. El-Mir MY, Nogueira V, Fontaine E, Averet N, Rigoulet M, Leverve X. Dimethylbiguanide inhibits cell effect targeted on the respiratory chain complex I. J Biol Chem. 2000;275:223-8.

  40. Pollak M. Metformin and other biguanides in oncology: Advancing the research agenda. Cancer Prev Res (Phila). 2010;3:1060-5.

  41. Hawley SA, Davidson M, Woods A, Davies SP, Beri RK, Carling D, et al. Characterization of the AMP-activated protein kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated. J Biol Chem. 1996;271:27879-87.

  42. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57-70.

  43. Zhang H, Pelzer AM, Kiang DT, Yee D. Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin. Cancer Res. 2007;67:391-7.

  44. Suissa S, Azoulay I. Metformine and the risk of cancer time-related bases on observational studies. Diabetes Care. 2012;35:2665-73.

  45. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, et al. Diabetes and Cancer: A Consensus Report. CA Cancer J Clin. 2010;60:207-21.

  46. Yun J, Rago C, Cheong I, Pagliarini R, Angenendt P, Rajagopalan H, et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells. Science. 2009;325:1555-9.

  47. Currie CJ, Poole CD, Gale EA. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes. Diabetologia. 2009;52:1766-77.

  48. Erickson K, Patterson RE, Flatt SW, Natarajan L, Parker BA, Heath DD, et al. Clinically defined type 2 diabetes mellitus and prognosis in early-stage breast cancer. J Clin Oncol. 2011;29:54-60.

  49. Peairs KS, Barone BB, Snyder CF, Yeh HC, Stein KB, Derr RL, et al. Diabetes mellitus and breast cancer outcomes: A systematic review and meta-analysis. J Clin Oncol. 2011;29:40-6.

  50. Wolin KY, Carson K, Colditz GA. Obesity and cancer. Oncologist. 2010;15:556-65.

  51. Viollet B, Gulgas B, Sanz N, Leclerc J. Cellular and molecular mechanism of metformin an overview. Cljn Sc. 2012;122:253-70.

  52. Macciò A, Madeddu C. Obesity, inflammation, and postmenopausal breast cancer: therapeutic implications. Sc World J. 2011;11:2020-36.

  53. Sánchez C, Ibáñez C, Klaassen J. Obesidad y cáncer: la tormenta perfecta. Rev Méd Chile. 2014;142:211-21.

  54. Colditz GA, Wolin KY, Gehlert S. Applying what we know to accelerate cancer prevention. Sci Transl Med. 2012;4:1-9.

  55. Key TJ, Spencer EA, Reeves GK. Symposium 1: Overnutrition: consequences and solutions. Obesity and cancer risk. Proc Nutr Soc. 2010;69:86-90.

  56. Luo J, Horn K, Okeene JK, Simon MS, Stefanick ML, Tong E, et al. Interaction between smoking and obesity and the risk of developing breast cancer among postmenopausal women: the Women's Health Initiative Observational Study. Am J Epidemiol. 2011;174:919-28.

  57. Azrad M, Demark-Whahnefreid W. The association between adiposity and cancer recurrence and survival. A review of recent literature. Curr Nutr Rep. 2014;3:9-15.

  58. Larsson SC, Wolk A. Obesity and the risk of gallbladder cancer: a metaanalysis. Br J Cancer. 2007;96:1457-61.

  59. Kuper H, Cramer DW, Titus L. Risk of ovarian cancer in the United States in relation to anthropometric measures: does the association depend on menopausal status? Cancer Causes Control. 2002;13:455-63.

  60. Leitzmann MF, Koebnick C, Danforth KN, Brinton LA, Moore SC, Hollenbeck AR, et al. Body mass index and risk of ovarian cancer. Cancer. 2009;115:812-22.

  61. Renehan A. Cáncer y tratamiento contra la diabetes: cinco años después de la noticia de última hora. Diabetes Voice. 2014;59:34-9.

  62. Orgel E, Mittelman SD. The links between insulin resistances, diabetes y cancer. Curr Diab Rep. 2013;13:213-22.




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