References

nogr

Экспериментальная и клиническая гастроэнтерология

Experimental and Clinical Gastroenterology

1682-8658

«Global Media Technologies»

10.31146/1682-8658-ecg-205-9-161-170

nogr-2053

Research Article

ОБЗОР

REVIEW

Метформин в профилактике колоректального рака при сахарном диабете

Metformin in the prevention of colorectal cancer with diabetes mellitus

https://orcid.org/0000-0001-8317-7765

Друк

Инна Викторовна

Druk

I. V.

drukinna@yandex.ru

Лялюкова

Елена Александровна

Lyalyukova

E. A.

noemail@neicon.ru

https://orcid.org/0000-0003-2408-2541

Фадеева

Елена Алексеевна

Fadeeva

E. A.

noemail@neicon.ru

ФГБОУ ВО «Омский государственный медицинский университет» Министерства здравоохранения Российской ФедерацииРоссияOmsk State Medical University of the Ministry of Health of the Russian FederationRussian Federation

2022

07102022

09161170

2022

Друк И.В., Лялюкова Е.А., Фадеева Е.А.

Druk I.V., Lyalyukova E.A., Fadeeva E.A.

Данная работа распространяется под лицензией Creative Commons Attribution 4.0.

This work is licensed under a Creative Commons Attribution 4.0 License.

https://www.nogr.org/jour/article/view/2053

Цель обзора- представить анализ современных литературных данных о перспективах использования онкопротекторного эффекта метформина при колоректальном раке. Метформин - препарат с многолетней историей, он является препаратом первой линии для лечения сахарного диабета 2 типа (СД2), а также наиболее часто назначаемым препаратом во всем мире. Современные исследования показывают, что помимо роли в контроле уровня глюкозы, метформин может снизить риск и смертность от ряда злокачественных новообразований, улучшить ответ пациентов с СД2 на некоторые виды лечения рака. Накопленные данные указывают на то, что метформин может быть кандидатным препаратом для медикаментозной профилактики колоректальногот рака

The purpose of the review is to present an analysis of current literature data on the prospects of using the oncoprotective effect of metformin in colorectal cancer. Metformin is a drug with a long history, it is a first-line drug for the treatment of type 2 diabetes mellitus (DM2), as well as the most commonly prescribed drug worldwide. Modern researches show that in addition to its role in glucose control, metformin can reduce the risk and mortality from some malignancies and improve the response of patients with DM2 to certain types of cancer treatment. Accumulated data indicate that metformin could be a candidate drug for drug prevention of colorectal cancer.

колоректальный ракметформинонкопротекция

colorectal cancermetformincancer prevention

References1

Cimmerman Ya. S. Colorectal cancer: state-of-the-art. RJGHC. 2012. Vol. 22 no. 4, pp.5-16. (In Russian) @@Циммерман Я. С. Колоректальный рак: современное состояние проблемы. Российский журнал гастроэнтерологии, гепатологии, колопроктологии, 2012. 22;4: C. 5-16.

Ferlay J., Colombet M., Soerjomataram I., et al. the global cancer incidence and mortality in 2018: GLOBOCAN sources and methods.Int J Cancer. 2019 Apr 15;144(8):1941-1953. doi: 10.1002/ijc.31937.

Biller L.H., Schrag D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA. 2021;325(7):669-685. doi:10.1001/jama.2021.0106.

Kaprin A. D., Starinskij V. V., Shahzadova A. O. Sostoyanie onkologicheskoj pomoshchi naseleniyu Rossii v 2019 godu [The state of oncological care to the population of Russia in 2019], 2020. (In Russian) Available at: https://glavonco.ru/cancer_register/Помощь%202019.pdf @@Каприн А. Д., Старинский В. В., Шахзадова А. О. Состояние онкологической помощи населению России в 2019 году, 2020. https://glavonco.ru/cancer_register/Помощь%202019.pdf

Siegel R.L., Miller K. D., Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019 Jan;69(1):7-34. doi: 10.3322/caac.21551.

Vekic J., Zeljkovic A., Stefanovic A., et al. Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents.Int J Mol Sci. 2021 Nov 17;22(22):12409. doi: 10.3390/ijms222212409.

Giouleme O., Diamantidis M. D., Katsaros M. G. Is diabetes a causal agent for colorectal cancer? Pathophysiological and molecular mechanisms. World J. Gastroenterol. 2011;17:444-448. doi: 10.3748/wjg.v17.i4.444

Hua F., Yu J. J., Hu Z. W. Diabetes and cancer, common threads and missing links. Cancer Lett. 2016;374:54-61. doi: 10.1016/j.canlet.2016.02.006.

Kamarudin M.N.A., Sarker M. M.R., Zhou J. R., Parhar I. Metformin in colorectal cancer: molecular mechanism, preclinical and clinical aspects. J Exp Clin Cancer Res. 2019;38(1):491. doi:10.1186/s13046-019-1495-2.

Berkovic M.C., Mikulic D., Bilic-Curcic I., Mrzljak A. How far along are we in revealing the connection between metformin and colorectal cancer?. World J Gastroenterol. 2021;27(14):1362-1368. doi:10.3748/wjg.v27.i14.1362.

Ashamalla M., Youssef I., Yacoub M., et al. Obesity, Diabetes and Gastrointestinal Malignancy: The role of Metformin and other Anti-diabetic Therapy. Glob J Obes Diabetes Metab Syndr. 2018;5(2):008-14. doi: 10.17352/2455-8583.000032

Hevroni G., Skwiersky S., Zhyvotovska A., McFarlane S. I. Metformin use and the Risk of Gastrointestinal Malignancies in Diabetic Populations: A Meta-Analysis.Int J Clin Endocrinol Metab. 2020.6(1): 035-041. doi:10.17352/ijcem.000052.

Lazarova D., Bordonaro M. Multifactorial causation of early onset colorectal cancer. J Cancer. 2021 Sep 24;12(22):6825-6834. doi:10.7150/jca.63676.

Bordonaro M., Lazarova D. Hypothesis: Obesity Is Associated with a Lower Mutation Threshold in Colon Cancer. J Cancer. 2015 Jul 15;6(9):825-31. doi: 10.7150/jca.12352.

Bailey C.E., Hu C. Y., You Y. N., et al. Increasing disparities in the age-related incidences of colon and rectal cancers in the United States, 1975-2010. JAMA Surg. 2015 Jan;150(1):17-22. doi: 10.1001/jamasurg.2014.1756.

Sung H., Siegel R. L., Rosenberg P. S., Jemal A. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. Lancet Public Health. 2019 Mar;4(3): e137-e147. doi: 10.1016/S2468-2667(18)30267-6.

Caudle A.S., Kim H. J., Tepper J. E., et al. Diabetes mellitus affects response to neoadjuvant chemoradiotherapy in the management of rectal cancer. Ann. Surg. Oncol. 2008;15:1931-1936. doi: 10.1245/s10434-008-9873-6.

Meyerhardt J.A., Catalano P. J., Haller D. G., et al. Impact of diabetes mellitus on outcomes in patients with colon cancer. J. Clin. Oncol. 2003;21:433-440. doi: 10.1200/JCO.2003.07.125.

Zhu B., Wu X., Wu B., et al. The relationship between diabetes and colorectal cancer prognosis: A meta-analysis based on the cohort studies. PLoS ONE. 2017;12: e0176068. doi: 10.1371/journal.pone.0176068.

Salani B., Del Rio A., Marini C., et al. Metformin, cancer and glucose metabolism. Endocr Relat Cancer. 2014;21(6): R461-71. doi: 10.1530/ERC-14-0284.

Zhu B., Qu S. The Relationship Between Diabetes Mellitus and Cancers and Its Underlying Mechanisms. Front Endocrinol (Lausanne). 2022;13:800995. doi:10.3389/fendo.2022.800995.

Rena G., Hardie D. G., Pearson E. R. The mechanisms of action of metformin. Diabetologia. 2017 Sep;60(9):1577-1585. doi: 10.1007/s00125-017-4342-z.

Bailey C. J. Metformin: historical overview. Diabetologia. 2017 Sep;60(9):1566-1576. doi: 10.1007/s00125-017-4318-z.

Sterne J. Du nouveau dans les antidiabétiques. La NN dimethylamine guanyl guanidine (N.N.D.G.) Maroc Med. 1957. 36:1295-1296.

Foretz M., Guigas B., Bertrand L., et al. Metformin: from mechanisms of action to therapies. Cell Metab. 2014 Dec 2;20(6):953-66. doi: 10.1016/j.cmet.2014.09.018.

UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) Lancet. 1998. 352:854-865.

Maruthur N.M., Tseng E., Hutfless S., et al. Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis. Ann Intern Med. 2016 Jun 7;164(11):740-51. doi: 10.7326/M15-2650.

Hostalek U., Gwilt M., Hildemann S. Therapeutic Use of Metformin in Prediabetes and Diabetes Prevention. Drugs. 2015 Jul;75(10):1071-94. doi: 10.1007/s40265-015-0416-8.

Vieira I.H., Barros L. M., Baptista C. F., et al. Recommendations for Practical Use of Metformin, a Central Pharmacological Therapy in Type 2 Diabetes. Clin Diabetes. 2022 Jan;40(1):97-107. doi: 10.2337/cd21-0043.

Druk I.V., Ryapolova E. A. Metformin: obnovelnnye rekomendacii i plejotropnyj potencial [Metformin: updated recommendations and pleiotropic potential] Terapiya - Therapy, 2016. no 4, pp. 79-64. (In Russ.) @@Друк И. В., Ряполова Е. А. Метформин: обновелнные рекомендации и плейотропный потенциал. Терапия. 2016. № 4, С. 44-51.

Druk I.V. [Metformin in the treatment of type II diabetes mellitus: a bestseller, not read to the end]. Lechashchij vrach - The attending physician, 2011. no 5, pp 79-84. (In Russ.) @@Друк И. В. Метформин в терапии сахарного диабета второго типа: бестселлер, не прочитанный до конца. Лечащий врач. 2011. № 5. C. 79-84.

Flory J., Lipska K. Metformin in 2019. JAMA. 2019 May 21;321(19):1926-1927. doi: 10.1001/jama.2019.3805.

Griffin S.J., Leaver J. K., Irving G. J. Impact of metformin on cardiovascular disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60(9):1620-1629. doi:10.1007/s00125-017-4337-9.

ClinicalTrials.gov. Investigation of Metformin in Pre-Diabetes on Atherosclerotic Cardiovascular OuTcomes (VA-IMPACT). 2019; ClinicalTrials.gov Identifier: NCT02915198; Available at: https://clinicaltrials.gov/ct2/show/NCT02915198 Access: 05.05.2021.

Lv Z., Guo Y. Metformin and Its Benefits for Various Diseases. Front Endocrinol (Lausanne). 2020 Apr 16;11:191. doi: 10.3389/fendo.2020.00191.

Traci E. LaMoia, Gerald I. Shulman. Cellular and Molecular Mechanisms of Metformin Action. Endocr Rev. 2021 Jan 28;42(1):77-96. doi: 10.1210/endrev/bnaa023.

Zhou G., Myers R., Li Y., et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001 Oct;108(8):1167-74. doi: 10.1172/JCI13505.

Demidova T. Y., Drozdova I. N. [Metformin: New Benefits Provided by Evidence-Based Medicine]. Effektivnaya farmakoterapiya - Effective pharmacotherapy, 2015. No 28, pp. 32-36. (In Russian) @@Демидова Т. Ю., Дроздова И. Н. Метформин: новые преимущества в свете доказательной медицины. Эффективная фармакотерапия. 2015. № 28. C.32-36.

Apostolova N., Iannantuoni F., Gruevska A., et al. Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions. Redox Biol. 2020 Jul;34:101517. doi: 10.1016/j.redox.2020.101517.

Vasamsetti S.B., Karnewar S., Kanugula A. K., et al. Metformin inhibits monocyte-to-macrophage differentiation via AMPK-mediated inhibition of STAT3 activation: potential role in atherosclerosis. Diabetes. 2015 Jun;64(6):2028-41. doi: 10.2337/db14-1225.

Cameron A. R., Morrison V. L., Levin D., et al. Anti-Inflammatory Effects of Metformin Irrespective of Diabetes Status. Circ Res. 2016 Aug 19; 119(5): 652-665. doi: 10.1161/CIRCRESAHA.116.308445.

Frantsiyants E. M., Surikova E. I., Kaplieva I. V., et al. Diabetes mellitus and cancer: a system of insulin-like growth factors. Problems of Endocrinology. 2021;67(5):34-42. (In Russ.) doi:10.14341/probl12741. @@Франциянц Е. М., Сурикова Е. И., Каплиева И. В. и соавт. Сахарный диабет и онкопатология: система инсулиноподобных факторов роста. Проблемы Эндокринологии, 2021;67(5), C. 34-42. doi:10.14341/probl12741.

Chen K., Li Y., Guo Z., et al. Metformin: current clinical applications in nondiabetic patients with cancer. Aging (Albany NY). 2020 Feb 18;12(4):3993-4009. doi: 10.18632/aging.102787.

Heckman-Stoddard B.M., DeCensi A., Sahasrabuddhe V. V., Ford L. G. Repurposing metformin for the prevention of cancer and cancer recurrence. Diabetologia. 2017;60(9):1639-1647. doi:10.1007/s00125-017-4372-6

Aljada A., Mousa S. A. Metformin and neoplasia: implications and indications. Pharmacol Ther. 2012;133:108-115.

Zaharenko L. Pharmacogenetics of efficiency and tolerance of the peroral antidiabetic drug metformin. 2015. Doctoral thesis. University of Latvia: Riga.; 177 р. Available: https://dspace.lu.lv/dspace/bitstream/handle/7/31319/298-51284-Zaharenko_Linda_lt05006.pdf Accessed: 05.05.2021

Zhang J. J., Zhang Q. S., Li Z. Q., et al. Metformin attenuates PD-L1 expression through activating Hippo signaling pathway in colorectal cancer cells. Am J Transl Res. 2019 Nov 15;11(11):6965-6976.

Saber M. M., Galal M. A., Ain-Shoka A.A., Shouman S. A.Combination of metformin and 5-aminosalicylic acid cooperates to decrease proliferation and induce apoptosis in colorectal cancer cell lines. BMC Cancer. 2016 Feb 19;16:126. doi: 10.1186/s12885-016-2157-9.

Anisimov V. N., Popovich I. G., Egormin P. A., et al. [Prospects of use of antidiabetic biguanides for cancer prevenention and treatment: results of preclinical studies]. Voprosy onkologii - questions of oncology, 2016. Vol. 62, no 2, pp. 234-244. (In Russ.) @@Анисимов В. Н., Попович И. Г., Егормин П. А. и соавт. Перспективы применения антидиабетических бигуанидов для профилактики и лечения рака: результаты доклинических испытаний. Вопросы онкологии. 2016. Т. 62 № 2, С. 234-244.

Vancura A., Bu P., Bhagwat M., et al. Metformin as an Anticancer Agent. Trends Pharmacol Sci. 2018;39(10):867-878. doi:10.1016/j.tips.2018.07.006

Kalender A., Selvaraj A., Kim S. Y., et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 2010 May 5;11(5):390-401. doi: 10.1016/j.cmet.2010.03.014.

Hosono K., Endo H., Takahashi H., et al. Metformin suppresses colorectal aberrant crypt foci in a short-term clinical trial. Cancer Prev Res (Phila). 2010;(3):1077-1083. doi: 10.1158/1940-6207.CAPR-10-0186.

Blandino G., Valerio M., Cioce M., et al. Metformin elicits anticancer effects through the sequential modulation of DICER and c-MYC. Nat Commun. 2012. 3:865. doi: 10.1038/ncomms1859. PMID: 22643892.

Elgendy M., Ciro M., Hosseini A., et al.Combination of hypoglycemia and metformin impairs tumor metabolic plasticity and growth by modulating the PP2A-GSK3beta-MCL-1 Axis. Cancer Cell. 2019. 35:798-815 doi: 10.1016/j.ccell.2019.03.007.

Zhang Z.J., Zheng Z. J., Kan H., et al. Reduced risk of colorectal cancer with metformin therapy in patients with type 2 diabetes: a meta-analysis. Diabetes Care. 2011;34(10):2323-2328. doi:10.2337/dc11-0512.

Franciosi M., Lucisano G., Lapice E., et al. Metformin therapy and risk of cancer in patients with type 2 diabetes: systematic review. PLoS One. 2013 Aug 2;8(8): e71583. doi: 10.1371/journal.pone.0071583.

He X.K., Su T. T., Si J. M., Sun L. M. Metformin Is Associated With Slightly Reduced Risk of Colorectal Cancer and Moderate Survival Benefits in Diabetes Mellitus: A Meta-Analysis. Medicine (Baltimore). 2016 Feb;95(7): e2749. doi: 10.1097/MD.0000000000002749.

Nie Z., Zhu H., Gu M. Reduced colorectal cancer incidence in type 2 diabetic patients treated with metformin: a meta-analysis. Pharm Biol. 2016 Nov;54(11):2636-2642. doi: 10.1080/13880209.2016.1176057.

Yang W.T., Yang H. J., Zhou J. G., Liu J. L. Relationship between metformin therapy and risk of colorectal cancer in patients with diabetes mellitus: a meta-analysis.Int J Colorectal Dis. 2020 Nov;35(11):2117-2131. doi: 10.1007/s00384-020-03704-w.

Ng C.W., Jiang A. A., Toh E. M.S., et al. Metformin and colorectal cancer: a systematic review, meta-analysis and meta-regression.Int J Colorectal Dis. 2020. 35, 1501-1512. doi: 10.1007/s00384-020-03676-x.

Hou Y.C., Hu Q., Huang J., et al. Metformin therapy and the risk of colorectal adenoma in patients with type 2 diabetes: A meta-analysis. Oncotarget. 2017;8(5):8843-8853.doi:10.18632/oncotarget.1363.

Mei Z.B., Zhang Z. J., Liu C. Y., et al. Survival benefits of metformin for colorectal cancer patients with diabetes: a systematic review and meta-analysis. PLoS One. 2014 Mar 19;9(3): e91818. doi: 10.1371/journal.pone.0091818.

Meng F., Song L., Wang W. Metformin Improves Overall Survival of Colorectal Cancer Patients with Diabetes: A Meta-Analysis. J Diabetes Res. 2017;2017:5063239. doi: 10.1155/2017/5063239.

Du L., Wang M., Kang Y., et al. Prognostic role of metformin intake in diabetic patients with colorectal cancer: An updated qualitative evidence of cohort studies. Oncotarget. 2017;8(16):26448-26459. doi:10.18632/oncotarget.14688.

Cheng Y., Chen Y., Zhou C., et al. For colorectal cancer patients with type II diabetes, could metformin improve the survival rate? A meta-analysis. Clin Res Hepatol Gastroenterol. 2020 Feb;44(1):73-81. doi: 10.1016/j.clinre.2019.06.009.

Wang Y., Xiao J., Zhao Y., et al. Effect of metformin on the mortality of colorectal cancer patients with T2DM: meta-analysis of sex differences.Int J Colorectal Dis. 2020 May;35(5):827-835. doi: 10.1007/s00384-020-03539-5.

Cunha Júnior A. D., Bragagnoli A. C., Costa F. O., Carvalheira J. B.C. Repurposing metformin for the treatment of gastrointestinal cancer. World J Gastroenterol. 2021 May 7;27(17):1883-1904. doi: 10.3748/wjg.v27.i17.1883.

The authors declare that there are no conflicts of interest present.