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环境病理学,毒理学和肿瘤学期刊
影响因子: 1.625 5年影响因子: 1.63 SJR: 0.402 SNIP: 0.613 CiteScore™: 2.3

ISSN 打印: 0731-8898
ISSN 在线: 2162-6537

环境病理学,毒理学和肿瘤学期刊

DOI: 10.1615/JEnvironPatholToxicolOncol.2019029388
pages 133-141

Metformin: A Salutary Candidate for Colorectal Cancer Treatment in Patients with Diabetes

Vijaya Paul Samuel
Department of Anatomy, RAK College of Medicine, RAK Medical and Health Sciences University, Ras Al Khaimah, UAE
Rajiv Dahiya
Laboratory of Peptide Research and Development, School of Pharmacy, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago, West Indies
Yogendra Singh
Department of Pharmaceutical Sciences, Mahatma Gandhi College of Pharmaceutical Sciences, Sitapura, Jaipur, India
Gaurav Gupta
School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, 302017, Jaipur, India
Sushil Kumar Sah
Birat Medical College, Biratnagar, Nepal
Shiva Kumar Gubbiyappa
School of Pharmacy, GITAM University, Hyderabad, India
Dinesh Kumar Chellappan
Department of Life Sciences, School of Pharmacy, International Medical University, Bukit Jalil, Kuala Lumpur, Malaysia 57000
Kamal Dua
Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney (UTS), Ultimo, NSW 2007, Australia; Centre for Inflammation, Centenary Institute, Sydney, NSW 2050, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) and School of Biomedical Sciences and Pharmacy, University of Newcastle (UoN), Callaghan, NSW 2308, Australia

ABSTRACT

The current study is a review of the literature on patients with diabetes who are diagnosed with colorectal cancer (CRC), encompassing recent research on CRC and the molecular level changes occurring in these patients on the basis of varying environmental as well as non-environmental factors. It has been noted that nearly 50% of all patients undergo the systemic treatment module; however, most of them exhibit drug resistance. In addition, targeted gene therapy has also been used in treatment but has been found to be effective only in patients with a specified molecular profile (or else this might lead to an increased risk of developing resistant mutations). This has led to increasing interest among researchers in finding innovative treatment options. Metformin, a biguanide, has been widely used in treating diabetes. The drug has been reportedly used in cases of hypothesis-generating retrospective population studies of diabetic patients showing reduced incidence of cancer. Metformin helps in reduction of excess insulin levels that possess various effects on cell signaling and metabolism. Nonetheless, there is need for an in-depth study on its molecular mechanism to fill any existing research gaps.

REFERENCES

  1. Kolligs FT. Diagnostics and epidemiology of colorectal cancer. Visceral Med. 2016;32(3):158-64.

  2. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. May 27 2006;367(9524):1747-1757.

  3. Zheng Y, Ley SH, Hu FB. Global aetiology and epidemiology of type 2 diabetes mellitus and its complications. Nature Rev Endocrinol. 2017;14:88.

  4. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. Mar 2015;65(2):87-108.

  5. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015. CA Cancer J Clin. 2015;65(1):5-29.

  6. Fleming M, Ravula S, Tatishchev SF, Wang HL. Colorectal carcinoma: pathologic aspects. J Gastrointest Oncol. 2012;3(3):153-73.

  7. Bhandari A, Woodhouse M, Gupta S. Colorectal cancer is a leading cause of cancer incidence and mortality among adults younger than 50 years in the USA: a SEER-based analysis with comparison to other young-onset cancers. J Invest Med. 2017;65(2):311-15.

  8. Shivashankar R, Tremaine WJ, Harmsen WS, Loftus EV, Jr. Incidence and prevalence of Crohn's disease and ulcerative colitis in Olmsted County, Minnesota from 1970 through 2010. Clin Gastroenterol Hepatol. 2017;15(6):857-63.

  9. Herrinton LJ, Liu L, Levin TR, Allison JE, Lewis JD, Velayos F. Incidence and mortality of colorectal adenocarcinoma in persons with inflammatory bowel disease from 1998 to 2010. Gastroenterology. 2012;143(2):382-89.

  10. Gonzalez N, Prieto I, del Puerto-Nevado L, Portal-Nunez S, Ardura JA, Corton M, Fernandez-Fernandez B, Aguilera O, Gomez-Guerrero C, Mas S, Moreno JA, Ruiz-Ortega M, Sanz AB, Sanchez-Nino MD, Rojo F, Vivanco F, Esbrit P, Ayuso C, Alvarez-Llamas G, Egido J, Garcia-Foncillas J, Ortiz A, Diabetes Cancer Connect Consortium. 2017 update on the relationship between diabetes and colorectal cancer: epidemiology, potential molecular mechanisms and therapeutic implications. Oncotarget. 2017;8(11):18456-85.

  11. Herrera C, Armanasco N, Garcia-Perez J, Ziprin P, Olejniczak N, Alcami J, Nuttall J, Shattock RJ. Maraviroc and reverse transcriptase inhibitors combinations as potential preexposure prophylaxis candidates. AIDS. 2016;30(7):1015-25.

  12. Giovannucci E, Harlan DM, Archer MC, Bergenstal RM, Gapstur SM, Habel LA, Pollak M, Regensteiner JG, Yee D. Diabetes and cancer: a consensus report. Diabetes Care. 2010;33(7):1674-85.

  13. American Diabetes A. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2010;33(Suppl 1): S62-69.

  14. Maahs DM, West NA, Lawrence JM, Mayer-Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am. 2010;39(3):481-97.

  15. Craig ME, Hattersley A, Donaghue KC. Definition, epidemiology and classification of diabetes in children and adolescents. Pediatr Diabetes. 2009;10(Suppl 12):3-12.

  16. Dabelea D, Mayer-Davis EJ, Saydah S, Imperatore G, Linder B, Divers J, Bell R, Badaru A, Talton JW, Crume T, Liese AD, Merchant AT, Lawrence JM, Reynolds K, Dolan L, Liu LL, Hamman RF. Prevalence of type 1 and type 2 diabetes among children and adolescents from 2001 to 2009. JAMA. 2014;311(17):1778-86.

  17. Kharroubi AT, Darwish HM. Diabetes mellitus: the epidemic of the century. World J Diabetes. 2015;6(6): 850-67.

  18. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000;106(4):473-81.

  19. Peeters PJHL, Bazelier MT, Leufkens HGM, de Vries F, De Bruin ML. The risk of colorectal cancer in patients with type 2 diabetes: associations with treatment stage and obesity. Diabetes Care. 2015;38(3):495-502.

  20. Tabak AG, Jokela M, Akbaraly TN, Brunner EJ, Kivimaki M, Witte DR. Trajectories of glycaemia, insulin sensitivity, and insulin secretion before diagnosis of type 2 diabetes: an analysis from the Whitehall II study. Lancet. 2009;373(9682):2215-21.

  21. Reaven GM. Role of insulin resistance in human disease. Diabetes. 1988;37(12):1595-1607.

  22. Mitrakou A, Kelley D, Mokan M, Veneman T, Pangburn T, Reilly J, Gerich J. Role of reduced suppression of glucose production and diminished early insulin release in impaired glucose tolerance. N Engl J Med. 1992;326(1):22-29.

  23. Pollak M. The insulin and insulin-like growth factor receptor family in neoplasia: an update. Nat Rev Cancer. 2012;12(3):159-69.

  24. The Cancer Genome Atlas Research N. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature. 2008;455(7216):1061-68.

  25. Murugan AK, Alzahrani A, Xing M. Mutations in critical domains confer the human mTOR gene strong tumorigenicity. J Biol Chem. Mar 1 2013;288(9):6511-21.

  26. Guertin DA, Sabatini DM. Defining the role of mTOR in cancer. Cancer Cell. 2007;12(1):9-22.

  27. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol. 2011;12(1):21-35.

  28. Khan KH, Yap TA, Yan L, Cunningham D. Targeting the PI3K-AKT-mTOR signaling network in cancer. Chinese J Cancer. 2013;32(5):253-65.

  29. Hara K, Maruki Y, Long X, Yoshino K, Oshiro N, Hidayat S, Tokunaga C, Avruch J, Yonezawa K. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell. 2002;110(2):177-189.

  30. Robbins CM, Tembe WA, Baker A, Sinari S, Moses TY, Beckstrom-Sternberg S, Beckstrom-Sternberg J, Barrett M, Long J, Chinnaiyan A, Lowey J, Suh E, Pearson JV, Craig DW, Agus DB, Pienta KJ, Carpten JD. Copy number and targeted mutational analysis reveals novel somatic events in metastatic prostate tumors. Genome Res. 2011;21(1):47-55.

  31. Samuels Y, Wang Z, Bardelli A, Silliman N, Ptak J, Szabo S, Yan H, Gazdar A, Powell SM, Riggins GJ, Willson JK, Markowitz S, Kinzler KW, Vogelstein B, Velculescu VE. High frequency of mutations of the PIK3CA gene in human cancers. Science. 2004;304(5670):554.

  32. Schwab U, Lauritzen L, Tholstrup T, Haldorssoni T, Riserus U, Uusitupa M, Becker W. Effect of the amount and type of dietary fat on cardiometabolic risk factors and risk of developing type 2 diabetes, cardiovascular diseases, and cancer: a systematic review. Food Nutr Res. 2014;58.

  33. Hellmann J, Zhang MJ, Tang Y, Rane M, Bhatnagar A, Spite M. Increased saturated fatty acids in obesity alter resolution of inflammation in part by stimulating prostaglandin production. J Immunol. Aug 1 2013;191(3):1383-92.

  34. Axelrod L. Insulin, prostaglandins, and the pathogenesis of hypertension. Diabetes. 1991;40(10):1223-27.

  35. Narasimha Das U. Lipoxins, resolvins, protectins, maresins and nitrolipids, and their clinical implications with specific reference to diabetes mellitus and other diseases: part II. Clin Lipidol. 2013;8(4):465-80.

  36. Das UN. Essential fatty acids and their metabolites could function as endogenous HMG-CoA reductase and ACE enzyme inhibitors, anti-arrhythmic, anti-hypertensive, anti-atherosclerotic, anti-inflammatory, cytoprotective, and cardioprotective molecules. Lipids Health Dis. 2008;7:37.

  37. Xu H, Fu J-L, Miao Y-F, Wang C-J, Han Q-F, Li S, Huang S-Z, Du S-N, Qiu Y-X, Yang J-C, Gustafsson J-A, Breyer RM, Zheng F, Wang N-P, Zhang X-Y, Guan Y-F. Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue. J Mol Cell Biol. 2016;8(6):518-29.

  38. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med. 2004;10(8):789-99.

  39. Breyer RM, Bagdassarian CK, Myers SA, Breyer MD. Prostanoid receptors: subtypes and signaling. Ann Rev Pharmacol Toxicol. 2001;41:661-90.

  40. Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of beta-catenin by human Axin and its association with the APC tumor suppressor, beta-catenin and GSK3 beta. Curr Biol. 1998;8(10):573-81.

  41. Wu J, Saint-Jeannet JP, Klein PS. Wnt-frizzled signaling in neural crest formation. Trends Neurosci. 2003; 26(1): 40-45.

  42. MacDonald BT, Tamai K, He X. Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell. 2009;17(1):9-26.

  43. Kim L, Kimmel AR. GSK3, a master switch regulating cell-fate specification and tumorigenesis. Curr Opin Genet Dev. Oct 2000;10(5):508-14.

  44. Rayasam GV, Tulasi VK, Sodhi R, Davis JA, Ray A. Glycogen synthase kinase 3: more than a namesake. Br J Pharmacol. 2009;156(6):885-98.

  45. McCubrey JA, Steelman LS, Bertrand FE, Davis NM, Abrams SL, Montalto G, D'Assoro AB, Libra M, Nicoletti F, Maestro R, Basecke J, Cocco L, Cervello M, Martelli AM. Multifaceted roles of GSK-3 and Wnt/beta-catenin in hematopoiesis and leukemogenesis: opportunities for therapeutic intervention. Leukemia. 2014;28(1):15-33.

  46. Xu C, Kim NG, Gumbiner BM. Regulation of protein stability by GSK3 mediated phosphorylation. Cell Cycle. 2009;8(24):4032-39.

  47. Fang D, Hawke D, Zheng Y, Xia Y, Meisenhelder J, Nika H, Mills GB, Kobayashi R, Hunter T, Lu Z. Phosphorylation of B-catenin by AKT promotes B-catenin transcriptional activity. J Biol Chem. 2007;282(15):11221-29.

  48. Castellone MD, Teramoto H, Williams BO, Druey KM, Gutkind JS. Prostaglandin E2 promotes colon cancer cell growth through a Gs-axin-beta-catenin signaling axis. Science. 2005;310(5753):1504-10.

  49. Ruvolo PP, Qiu Y, Coombes KR, Zhang N, Neeley ES, Ruvolo VR, Hail N, Borthakur G, Konopleva M, Andreeff M, Kornblau SM. Phosphorylation of GSK3a/B correlates with activation of AKT and is prognostic for poor overall survival in acute myeloid leukemia patients. BBA Clin. 2015;4:59-68.

  50. Xia X, Batra N, Shi Q, Bonewald L, Sprague E, Jiang J. Prostaglandin promotion of osteocyte gap junction function through transcriptional regulation of connexin 43 by glycogen synthase kinase 3/ -catenin signaling. Mol Cell Biol. 2009;30:206-19.

  51. Goessling W, North TE, Loewer S, Lord AM, Lee S, Stoick-Cooper CL, Weidinger G, Puder M, Daley GQ, Moon RT, Zon LI. Genetic interaction of PGE2 and Wnt signaling regulates developmental specification of stem cells and regeneration. Cell. 2009;136(6):1136-47.

  52. Inoki K, Ouyang H, Zhu T, Lindvall C, Wang Y, Zhang X, Yang Q, Bennett C, Harada Y, Stankunas K, Wang CY, He X, MacDougald OA, You M, Williams BO, Guan KL. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth. Cell. 2006;126(5):955-68.

  53. Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB. Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients. Proc Natl Acad Sci U S A. 1987;84(23):8628-32.

  54. Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH. Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells. Proc Natl Acad Sci USA. 1987; 84(11):3881-85.

  55. Singh Y, Gupta G, Shrivastava B, Dahiya R, Tiwari J, Ashwathanarayana M, Sharma RK, Agrawal M, Mishra A, Dua K. Calcitonin gene-related peptide (CGRP): A novel target for Alzheimer.

  56. van Rossum D, Hanisch UK, Quirion R. Neuroanatomical localization, pharmacological characterization and functions of CGRP, related peptides and their receptors. Neurosci Biobehav Rev. 1997;21(5):649-78.

  57. Edvinsson L. The trigeminovascular pathway: role of CGRP and CGRP receptors in migraine. Headache. 2017; 57(Suppl 2):47-55.

  58. MaassenVanDenBrink A, Terwindt GM, van den Maagdenberg AMJM. Calcitonin gene-related peptide (receptor) antibodies: an exciting avenue for migraine treatment. Genome Med. 2018;10:10.

  59. Parlapiano C, Minniti G, Primi F, Campana E. Calcitonin gene-related peptide in diabetes mellitus type 2: a possible etiopathogenetic role. Riv Eur Sci Med Farmacol. 1995;17(1):35-39.

  60. Kaleczyc JGAJ. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma. Folia Histochem Cytobiol. 2010;48(3):475-83.

  61. Campos CA, Bowen AJ, Schwartz MW, Palmiter RD. Parabrachial CGRP neurons control meal termination. Cell Metab. 2016;23(5):811-820.

  62. Sardi C, Zambusi L, Finardi A, Ruffini F, Tolun AA, Dickerson IM, Righi M, Zacchetti D, Grohovaz F, Provini L, Furlan R, Morara S. Involvement of calcitonin gene-related peptide and receptor component protein in experimental autoimmune encephalomyelitis. J Neuroimmunol. 2014;271(1):18-29.

  63. Gherardini G, Gurlek A, Milner SM, Matarasso A, Evans GR, Jernbeck J, Lundeberg T. Calcitonin gene-related peptide improves skin flap survival and tissue inflammation. Neuropeptides. 1998;32(3):269-73.

  64. Makowska K, Gonkowski S. The influence of inflammation and nerve damage on the neurochemical characterization of calcitonin gene-related peptide-like immunoreactive (CGRP-LI) neurons in the enteric nervous system of the porcine descending colon. Int J Mol Sci. 2018;19(2):548.

  65. Balemba OB, GrONdahl ML, Mbassa GK, Semuguruka WD, Hay-Smith A, Skadhauge E, Dantzer V. The organisation of the enteric nervous system in the submucous and mucous layers of the small intestine of the pig studied by VIP and neurofilament protein immunohistochemistry. J Anat. 1998;192(Pt 2):257-267.

  66. Hens J, Schrodl F, Brehmer A, Adriaensen D, Neuhuber W, Scheuermann DW, Schemann M, Timmermans JP. Mucosal projections of enteric neurons in the porcine small intestine. J Comp Neurol. 2000;421(3):429-36.

  67. Lomax AE, Furness JB. Neurochemical classification of enteric neurons in the guinea-pig distal colon. Cell Tissue Res. 2000;302(1):59-72.

  68. Wang LH, Zhou SX, Li RC, Zheng LR, Zhu JH, Hu SJ, Sun YL. Serum levels of calcitonin gene-related peptide and substance P are decreased in patients with diabetes mellitus and coronary artery disease. J Int Med Res. 2012;40(1):134-40.

  69. Pettersson M, Ahren B, Bottcher G, Sundler F. Calcitonin gene-related peptide: occurrence in pancreatic islets in the mouse and the rat and inhibition of insulin secretion in the mouse. Endocrinology. 1986;119(2):865-69.

  70. Yuan LJ, Qin Y, Wang L, Zeng Y, Chang H, Wang J, Wang B, Wan J, Chen SH, Zhang QY, Zhu JD, Zhou Y, Mi MT. Capsaicin-containing chili improved postprandial hyperglycemia, hyperinsulinemia, and fasting lipid disorders in women with gestational diabetes mellitus and lowered the incidence of large-for-gestational-age newborns. Clin Nutr. 2016;35(2):388-93.

  71. Goto A, Noda M, Sawada N, Kato M, Hidaka A, Mizoue T, Shimazu T, Yamaji T, Iwasaki M, Sasazuki S, Inoue M, Kadowaki T, Tsugane S. High hemoglobin A1c levels within the non-diabetic range are associated with the risk of all cancers. Int J Cancer. 2016;138(7):1741-53.

  72. Godlewski J, Kaleczyc J. Somatostatin, substance P and calcitonin gene-related peptide-positive intramural nerve structures of the human large intestine affected by carcinoma. Folia Histochem Cytobiol. 2010;48(3): 475-83.

  73. Umoh NA, Walker RK, Millis RM, Al-Rubaiee M, Gangula PR, Haddad GE. Calcitonin gene-related peptide regulates cardiomyocyte survival through regulation of oxidative stress by PI3K/Akt and MAPK signaling pathways Ann Clin Exp Hyper. 2014;2(1):1007.

  74. Umoh NA, Walker RK, Millis RM, Al-Rubaiee M, Gangula PR, Haddad GE. Calcitonin gene-related peptide regulates cardiomyocyte survival through regulation of oxidative stress by PI3K/Akt and MAPK signaling pathways. Ann Clin Exp Hyper. 2014;2(1):1007.

  75. Dang H, Yang L, Wang S, Fang F, Xu F. Calcitonin gene-related peptide ameliorates hyperoxia-induced lung injury in neonatal rats. Tohoku J Exp Med. 2012;227(2):129-38.

  76. Hara M, Takeba Y, Watanabe M, Ohta Y, Ohtsubo T, Kumai T, Matsumoto N. Calcitonin gene-related peptide inhibits tumor cell proliferation of hepatocellular carcinoma cells through the Ras/MEK/ERK pathway. J St Marianna University. 2015;6(2):263-72.

  77. Kinaan M, Ding H, Triggle CR. Metformin: An Old drug for the treatment of diabetes but a new drug for the protection of the endothelium. Med Princ Pract. 2015;24(5):401-15.

  78. Bailey CJ. Metformin: historical overview. Diabetologia. 2017;60(9):1566-76.

  79. Bailey CJ, Turner RC. Metformin. N Engl J Med. 1996;334(9):574-79.

  80. Pollak MN. Investigating metformin for cancer prevention and treatment: the end of the beginning. Cancer Discov. 2012;2(9):778-90.

  81. Pernicova I, Korbonits M. Metformin-mode of action and clinical implications for diabetes and cancer. Nat Rev Endocrinol. 2014;10(3):143-56.

  82. Kahn BB, Alquier T, Carling D, Hardie DG. AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism. Cell Metab. 2005;1(1):15-25.

  83. Kim EK, Miller I, Aja S, Landree LE, Pinn M, McFadden J, Kuhajda FP, Moran TH, Ronnett GV. C75, a fatty acid synthase inhibitor, reduces food intake via hypothalamic AMP-activated protein kinase. J Biol Chem. 2004;279(19):19970-76.

  84. Minokoshi Y, Alquier T, Furukawa N, Kim YB, Lee A, Xue B, Mu J, Foufelle F, Ferre P, Birnbaum MJ, Stuck BJ, Kahn BB. AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature. 2004;428(6982):569-74.

  85. Andersson U, Filipsson K, Abbott CR, Woods A, Smith K, Bloom SR, Carling D, Small CJ. AMP-activated protein kinase plays a role in the control of food intake. J Biol Chem. 2004;279(13):12005-08.

  86. Bond P. Regulation of mTORC1 by growth factors, energy status, amino acids and mechanical stimuli at a glance. J Int Soc Sports Nutr. 2016;13:8.

  87. Shaw RJ, Cantley LC. Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature. 2006; 441(7092):424-30.

  88. Danaher RN, Loomes KM, Leonard BL, Whiting L, Hay DL, Xu LY, Kraegen EW, Phillips AR, Cooper GJ. Evidence that alpha-calcitonin gene-related peptide is a neurohormone that controls systemic lipid availability and utilization. Endocrinology. 2008;149(1):154-60.

  89. Palmiter RD. The para\brachial nucleus: CGRP neurons function as a general alarm. Trends Neurosci. 2018; 41(5):280-93.

  90. Herrmann-Rinke C, McGregor GP, Goke B. Calcitonin gene-related peptide potently stimulates glucagon-like peptide-1 release in the isolated perfused rat ileum. Peptides. 2000;21(3):431-37.

  91. Afzal M, Kazmi I, Gupta G, Rahman M, Kimothi V, Anwar F. Preventive effect of metformin against N-nitrosodiethylamine-initiated hepatocellular carcinoma in rats. Saudi Pharm J. 2012;20(4):365-70.

  92. Liu Q, Tong D, Liu G, Gao J, Wang L-a, Xu J, Yang X, Xie Q, Huang Y, Pang J, Wang L, He Y, Zhang D, Ma Q, Lan W, Jiang J. Metformin inhibits prostate cancer progression by targeting tumor-associated inflammatory infiltration. Clin Cancer Res. 2018;24(22):5622-34.

  93. Gupta G, Chellappan D, Mishra A, Malipeddi H, Dua K. A clinical update on metformin and lung cancer in diabetic patients. Panminerva Medica. 2018;60(2):70-75.


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