Pleiotropic Effects of Metformin: Antioncogenic Action (Literature Review)

V.I. Pankiv

Abstract


Diabetes mellitus (DM) is associated with increased risk of cancers of some localizations and a moderate increase in cancer death. Leading pathogenetic role in the relationship of DM and malignant disease belongs to chronic hyperinsulinemia, mediated by a number of molecular mechanisms described in detail in the review. Metformin improves insulin sensitivity and reduces hyperinsulinemia, and has anti-cancer effect. In addition to indirect effects on insulin resistance of antitumor effect, metformin can directly inhibit the growth and proliferation of cancer cells through stimulation of AMP kinase. Antiproliferative effect of metformin on breast cancer and ovarian cancer was confirmed in a number of experimental and clinical studies. To clarify the mechanisms of action and effects of metformin in oncology practice, a number of studies is being conducted and/or planned, particularly in all subtypes of breast cancer. Confirmation of anti-tumor efficacy of metformin will help to expand the scope of its application in practical medicine and, in particular, in clinical oncology.


Keywords


diabetes mellitus; cancer; metformin

References


Colagiuri S. Diabesity: thyrapeutic options / S. Colagiuri // Diabetes Obes. Metab. — 2010. — Vol. 12, № 6. — P. 463-473.

Hjartåker A. Obesity and diabetes epidemics: cancer repercussions / A. Hjartåker, H. Langseth, E. Weiderpass // Adv. Exp. Med. Biol. — 2008. — Vol. 630. — P. 72-93.

Vigneri P. Diabetes and cancer / P. Vigneri, F. Frasca, L. Sciacca [et al.] // Endocr. Relat. Cancer. — 2009. — Vol. 16, № 4. — P. 1103-1123.

La Vecchia C. Overweight, obesity, diabetes, and risk of breast cancer: interlocking pieces of the puzzle / C. La Vecchia, S.H. Giordano, G.N. Hortobagyi, B. Chabner // Oncologist. — 2011. — Vol. 16, № 6. — P. 726-729.

Wotton C.J. Cancer in patients admitted to hospital with diabetes mellitus aged 30 years and over: record linkage studies / C.J. Wotton, D.G. Yeates, M.J. Goldacre // Diabetologia. — 2011. — Vol. 54, № 3. — P. 527-534.

Richardson L.C. Therapy insight: influence of type 2 diabetes on the development, treatment and outcomes of cancer / L.C. Richardson, L.A. Pollack // Nat. Clin. Pract. Oncol. — 2005. — Vol. 2, № 1. — P. 48-53.

Barone B.B. Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis / B.B. Barone, H.C. Ueh, C.F. Snyder [et al.] // JAMA. — 2008. — Vol. 300, № 23. — P. 2754-2764.

Shu X. Cancer risk among patients hospitalized for Type 1 diabetes mellitus: a population-based cohort study in Sweden / X. Shu, J. Ji, X. Li [et al.] // Diabet. Med. — 2010. — Vol. 27, № 7. — P. 791-797.

Бернштейн Л.М. Диабет, ожирение и онкологическая заболеваемость: риски и антириски / Л.М. Бернштейн // Сахарный диабет. — 2012. — № 4. — С. 81-88.

Calle E.E. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms / E.E. Calle, R. Kaaks // Nat. Rev. Cancer. — 2004. — Vol. 4, № 8. — P. 579-591.

Calle E.E. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults / E.E. Calle, C. Rodriguez, K. Walker-Thurmond, M.J. Thun // N. Engl. J. Med. — 2003. — Vol. 348, № 17. — P. 1625-1638.

Evans J.M.M. Metformin and reduced risk of cancer in diabetic patients / J.M.M. Evans, L.A. Donnelly, A.M. Emslie-Smith [et al.] // BMJ. — 2005. — Vol. 330, № 7503. — P. 1304-1305.

Bowker S.L. Increased cancer-related mortality for patients with type 2 diabetes who use sulfonylureas or insulin / S.L. Bowker, S.R. Majumdar, P. Veugelers, J.A. Johnson // Diabetes Care. — 2006. — Vol. 29, № 2. — P. 254-258.

Landman G.W.D. Metformin associated with lower cancer mortality in type 2 diabetes / G.W.D. Landman, N. Kleefstra, K.J.J. van Hateren [et al.] // Diabetes Care. — 2010. — Vol. 33, № 2. — P. 322-326.

Oliveria S.A. Cancer incidence among patients treated with antidiabetic pharmacotherapy / S.A. Oliveria, C.E. Koro, M.U. Yood, M. Sowell // Diabetes. Metabol. Syndrome: Clin. Res. Reviews. — 2008. — Vol. 2. — Р. 47-57.

Donadon V. Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease / V. Donadon, M. Balbi, M. Ghersetti [et al.] // World J. Gastroenterol. — 2009. — Vol. 15, № 20. — Р. 2506-2511.

Currie C.J. The influence of glucose-lowering therapies on cancer risk in type 2 diabetes / C.J. Currie, C.D. Poole, E.A. Gale // Diabetologia. — 2009. — Vol. 52, № 9. — Р. 1766-1777.

Wright J.L. Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study / J.L. Wright, J.L. Stanford // Cancer Causes Control. — 2009. — Vol. 20, № 9. — P. 1617-1622.

Smith U. Does diabetes therapy influence the risk of cancer? / U. Smith, E.A. Gale // Diabetologia. — 2009. — Vol. 52, № 9. — Р. 1699-1708.

Phoenix K.N. Dietary energy availability affects primary and metastatic breast cancer and metformin efficacy / K.N. Phoenix, F. Vumbaca, M.M. Fox [et al.] // Breast Cancer Res. Treat. — 2010. — Vol. 123, № 2. — P. 333-344.

Libby G. New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes / G. Libby, L.A. Donnely, P.T. Donnan [et al.] // Diabetes Care. — 2009. — Vol. 32. — P. 1620-1625.

Zhou G. Role of AMP-activated protein kinase in mechanism of metformin action / G. Zhou, R. Myers, Y. Li [et al.] // J. Clin. Invest. — 2001. — Vol. 108, № 8. — Р. 1167-1174.

Shackelford D.B. The LKB1-AMPK pathway: metabolism and growth control in tumour suppression / D.B. Shackelford, R.J. Shaw // Nat. Rev. Cancer. — 2009. — Vol. 9, № 8. — P. 563-575.

Cazzaniga M. Is it time to test metformin in breast clinical trials? / M. Cazzaniga, B. Bonanni, A. Guerrieri-Gonzaga, A. Decensi // Cancer Epidemiol. Biomarkers Prev. — 2009. — Vol. 18, № 3. — Р. 701-705.

Bojkova B. Metformin in chemically-induced mammary carcinogenesis in rats / B. Bojkova, P. Orendas, M. Garajova [et al.] // Neoplasma. — 2009. — Vol. 56, № 3. — Р. 269-274.

Dowling R.J. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells / R.J. Dowling, M. Zakikhani, I.G. Fantus [et al.] // Cancer Res. — 2007. — Vol. 67. — P. 10804-10812.

Liu B. Metformin induces unique biological and molecular responses in triple negative breast cancer cells / B. Liu, Z. Fan, S.M. Edgerton [et al.] // Cell Cycle. — 2009. — Vol. 8. — P. 2031-2040.

Brown K.A. Metformin inhibits aromatase expression in primary human breast adipose stromal cells / K.A. Brown, E.R. Simpson // Cancer. Res. — 2009. — Vol. 69 (Suppl.). — 690 s.

Session D.R. Treatment of atypical endometrial hyperplasia with an insulin-sensitizing agent / D.R. Session, K.R. Kalli, I.S. Tummon [et al.] // Gynecol. Oncol. — 2003. — Vol. 17. — P. 405-407.

Jiralerspong S. Metformin and pathologic complete responses to neoadjuvant chemotherapy in diabetic patients with breast cancer / S. Jiralerspong, S.L. Palla, S.H. Giordano [et al.] // J. Clin. Oncol. — 2009. — Vol. 27. — Р. 3297-3302.

Martin-Castillo B. Incorporating the antidiabetic drug metformin in HER2-positive breast cancer treated with neo-adjuvant chemotherapy and trastuzumab: an ongoing clinical-translational research experience at the Catalan Institute of Oncology / B. Martin-Castillo, J. Dorca, A. Vazquez-Martin [et al.] // Ann. Oncol. — 2010. — Vol. 21, № 1. — Р. 187-189.

Soranna D. Cancer risk associated with use of metformin and sulfonylurea in type 2 diabetes: a meta-analysis / D. Soranna, L. Scotti, A. Zambon [et al.] // Oncologist. — 2012. — Vol. 17, № 6. — P. 813-822.

Zhang H. Metformin and reduced risk of hepatocellular carcinoma in diabetic patients: a meta-analysis / H. Zhang, C. Gao, L. Fang [et al.] // Scand. J. Gastroenterol. — 2012. — № 11.

Дедов И.И. Потенциальные возможности метформина в профилактике и лечении онкологических заболеваний у больных сахарным диабетом 2 типа / И.И. Дедов, С.А. Бутрова, М.А. Берковская // Ожирение и метаболизм. — 2011. — № 1. — С. 40-49.

Chen G. Metformin inhibits growth of thyroid carcinoma cells, suppresses self-renewal of derived cancer stem cells, and potentiates the effect of chemotherapeutic agents / G. Chen, S. Xu, K. Renko, M. Derwahl // J. Clin. Endocrinol. Metab. — 2012. — Vol. 97, № 4. — P. 510-520.

Rezzónico J. Metformin treatment for small benign thyroid nodules in patients with insulin resistance / J. Rezzónico, M. Rezzónico, E. Pusiol [et al.] // Metab. Syndr. Relat. Disord. — 2011. — Vol. 9, № 1. — P. 69-75.

Кондратьева Л.В. Бигуаниды в терапии сахарного диабета / Под ред. А.С. Аметова. — М.: Планида,

— 48 с.




DOI: https://doi.org/10.22141/2224-0721.1.49.2013.84051

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