Применение метформина - целевая метаболическая терапия в онкологии

Автор: Шатова Ольга П., Каплун Дарья С., Зинкович Игорь И.

Журнал: Злокачественные опухоли @malignanttumors

Статья в выпуске: 2 (23), 2017 года.

Бесплатный доступ

Общеизвестно широкое применение метформина для лечения сахарного диабета II типа. Однако в многочисленных эпидемиологических исследованиях было показано, что больные, принимавшие метформин, реже болели раком различной локализации и имели лучший прогноз по выживаемости. Многие исследователи считают метформин таргетным метаболическим препаратом, который имеет множество целей: действует на митохондрии, влияет на внутриклеточный сигналинг, блокирует каналы, тормозит образование эндотелиального и тромбоцитарного факторов роста, снижает уровень витаминов, вовлеченных в синтез нуклеотидов и аминокислот и пр. Также установлено, что метформин относится к группе «метабостемных» препаратов, то есть действует на раковые стволовые клетки, блокируя их деление. Нами проведено обзорное исследование, которое освещает важнейшие механизмы и области применения метформина. Изучение применения данного препарата в онкологии позволит понять патогенетические мишени метаболической терапии и профилактики онкопатологий.

Еще

Метформин, рак, метилирование, фосфолипиды, раковые стволовые клетки, map-киназа, гликолиз, витамин в12, vitamin в12

Короткий адрес: https://sciup.org/140223043

IDR: 140223043 | DOI: 10.18027/2224-5057-2017-2-83-89

Список литературы Применение метформина - целевая метаболическая терапия в онкологии

Yu T., Wang C., Yang J., Guo Y., Wu Y., Li X. Metformin inhibits SUV39H1-mediated migration of prostate cancer cells, Oncogenesis, 2017, Vol. 6, No. 5, p. e324.
Cho Y. H., Ko B. M., Kim S. H., Myung Y. S., Choi J. H., Han J. P. et al. Does metformin affect the incidence of colonic polyps and adenomas in patients with type 2 diabetes mellitus? Intest. Res., 2014, Vol. 12, No. 2, pp. 139-145.
Hense H. W., Geier A. S. Re: "reduced risk of lung cancer with metformin therapy in diabetic patients: a systematic review and metaanalysis", Am. J. Epidemiol., 2014, Vol. 180, No. 11, pp. 1130-1131.
Schuler K. M., Rambally B. S., DiFurio M. J., Sampey B. P., Gehrig P. A., Makowski L. et al. Antiproliferative and metabolic effects of metformin in a preoperative window clinical trial for endometrial cancer, Cancer Med., 2015, Vol. 4, No. 2, pp. 161-173.
Gong J., Robbins L. A., Lugea A., Waldron R. T., Jeon C. Y., Pandol S. J. Diabetes, pancreatic cancer, and metformin therapy, Front. Physiol., 2014, Vol. 5, p. 426.
Gritti M., Wurth R., Angelini M., Barbieri F., Peretti M., Pizzi E. et al. Metformin repositioning as antitumoral agent: selective antiproliferative effects in human glioblastoma stem cells, via inhibition of CLIC1-mediated ion current, Oncotarget, 2014, Vol. 5, No. 22, pp. 11252-11268.
Daugan M., Dufay W. A., d'Hayer B., Boudy V. Metformin: An anti-diabetic drug to fight cancer, Pharmacol. Res., 2016, Vol. 113 (Pt. A), pp. 675-685.
Falah R. R., Talib W. H., Shbailat S. J. Combination of metformin and curcumin targets breast cancer in mice by angiogenesis inhibition, immune system modulation and induction of p53 independent apoptosis, Ther. Adv. Med. Oncol., 2017, Vol. 9, No. 4, pp. 235-252.
Abo-Elmatty D. M., Ahmed E. A., Tawfik M. K., Helmy S. A. Metformin enhancing the antitumor efficacy of carboplatin against Ehrlich solid carcinoma grown in diabetic mice: Effect on IGF-1 and tumoral expression of IGF-1 receptors, Int. Immunopharmacol., 2017, Vol. 44, pp. 72-86.
Shatova O. P., Butenko E. V., Khomutov E. V., Kaplun D. S., Sedakov I. E., Zinkovych I. I. Metformin impact on purine metabolism in breast cancer, Biomed. Khim., 2016, Vol. 62, No. 3, pp. 302-305.
Janzer A., German N. J., Gonzalez-Herrera K. N., Asara J. M., Haigis M. C., Struhl K. Metformin and phenformin deplete tricarboxylic acid cycle and glycolytic intermediates during cell transformation and NTPs in cancer stem cells, Proc. Natl. Acad. Sci., USA, 2014, Vol. 111, No. 29, pp. 10574-10579.
Fuentes-Mattei E., Velazquez-Torres G., Phan L., Zhang F., Chou P. C., Shin J. H. et al. Effects of obesity on transcriptomic changes and cancer hallmarks in estrogen receptor-positive breast cancer, J. Natl. Cancer Inst., 2014, Vol. 106, No. 7.
Kolb R., Phan L., Borcherding N., Liu Y., Yuan F., Janowski A. M. et al. Obesity-associated NLRC4 inflammasome activation drives breast cancer progression, Nat. Commun., 2016, Vol. 7: 13007.
Menendez J. A., Joven J. Energy metabolism and metabolic sensors in stem cells: the metabostem crossroads of aging and cancer, Adv. Exp. Med. Biol., 2014, No. 824, pp. 117-140.
Kourelis T. V., Siegel R. D. Metformin and cancer: new applications for an old drug, Med. Oncol., 2012, Vol. 29, No. 2, pp. 1314-1327.
Damjanovic A., Matic I. Z., Ethordic M., Ethurovic M. N., Nikolic S., Roki K. et al. Metformin effects on malignant cells and healthy PBMC; the influence of metformin on the phenotype of breast cancer cells, Pathol. Oncol. Res., 2015, Vol. 21, No. 3, pp. 605-612.
Snima K. S., Pillai P., Cherian A. M., Nair S. V., Lakshmanan V. K. Anti-diabetic drug metformin: challenges and perspectives for cancer therapy, Curr. Cancer Drug Targets, 2014, Vol. 14, No. 8, pp. 727-736.
Pulito C., Donzelli S., Muti P., Puzzo L., Strano S., Blandino G. MicroRNAs and cancer metabolism reprogramming: the paradigm of metformin, Ann. Transl. Med., 2014, Vol. 2, No. 6, p. 58.
Snima K. S., Jayakumar R., Unnikrishnan A. G., Nair S. V., Lakshmanan V. K. O-carboxymethyl chitosan nanoparticles for metformin delivery to pancreatic cancer cells, Carbohydr. Polym., 2012, Vol. 89, No. 3, pp. 1003-1007.
Wurth R., Barbieri F., Florio T. New molecules and old drugs as emerging approaches to selectively target human glioblastoma cancer stem cells, Biomed. Res. Int., 2014, Vol. 2014, 126586.
Zhao D., Long X. D., Lu T. F., Wang T., Zhang W. W., Liu Y. X. et al. Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma, Int. J. Cancer, 2015, Vol. 136, No. 11, pp. 2556-2565.
Zhang J., Shen C., Wang L., Ma Q., Xia P., Qi M. et al. Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4, Biochem. Biophys. Res. Commun., 2014, Vol. 452, No. 3, pp. 746-752.
Bao B., Azmi A. S., Ali S., Zaiem F., Sarkar F. H. Metformin may function as anti-cancer agent via targeting cancer stem cells: the potential biological significance of tumor-associated miRNAs in breast and pancreatic cancers, Ann. Transl. Med., 2014, Vol. 2, No. 6, p. 59.
Zhong T., Men Y., Lu L., Geng T., Zhou J., Mitsuhashi A. et al. Metformin alters DNA methylation genome-wide via the H19/SAHH axis, Oncogene, 2017, Vol. 36, No. 17, pp. 2345-2354.
Uehara T., Mitsuhashi A., Tsuruoka N., Shozu M. Metformin potentiates the anticancer effects of cisplatin under normoxic conditions in vitro, Oncol. Rep., 2015, Vol. 33, No. 2, pp. 744-750.
Baranov V. S., Glotov O. S., Baranova E. V. Genetic and epigenetic news in gerontology, Adv. Gerontol., 2014, Vol. 27, No. 2, pp. 247-256.
Liu C., Zeng X., Li Y., Ma H., Song J., Li Y. et al. Investigation of hypoglycemic, hypolipidemic and antinephritic activities of Paecilomyces tenuipesN45 in diet/streptozotocininduced diabetic rats, Mol. Med. Rep., 2017, Vol. 15, No. 5, pp. 2807-2813.
Smith T. A., Phyu S. M. Metformin Decouples Phospholipid Metabolism in Breast Cancer Cells, PLoS One, 2016, Vol. 11, No. 3, e0151179.
Huang Y., Fu J. F., Shi H. B., Liu L. R. Metformin prevents non-alcoholic fatty liver disease in rats: role of phospholipase A2/lysophosphatidylcholine lipoapoptosis pathway in hepatocytes, Zhonghua Er Ke Za Zhi, 2011, Vol. 49, No. 2, pp. 139-145.
Luengo A., Sullivan L. B., Heiden M. G. Understanding the complex-I-ty of metformin action: limiting mitochondrial respiration to improve cancer therapy, BMC Biol., 2014, Vol. 12, p. 82.
Son H. J., Lee J., Lee S. Y., Kim E. K., Park M. J., Kim K. W. et al. Metformin attenuates experimental autoimmune arthritis through reciprocal regulation of Th17/Treg balance and osteoclastogenesis, Mediators Inflamm., 2014, Vol. 2014, p. 973986.
Wahdan-Alaswad R. S., Cochrane D. R., Spoelstra N. S., Howe E. N., Edgerton S. M., Anderson S. M. et al. Metformin-induced killing of triple-negative breast Cancer cells is mediated by reduction in fatty acid synthase via miRNA-193bб Horm. Cancer, 2014, Vol. 5, No. 6, pp. 374-389.
Yang Q., Zhang T., Wang C., Jiao J., Li J., Deng Y. Coencapsulation of epirubicin and metformin in PEGylated liposomes inhibits the recurrence of murine sarcoma S180 existing CD133+ cancer stem-like cells, Eur. J. Pharm. Biopharm., 2014, Vol. 88, No. 3, pp. 737-745.
Damjanovic A., Matic I. Z., Ethordic M., Ethurovic M. N., Nikolic S., Roki K. et al. Metformin effects on malignant cells and healthy PBMC; the influence of metformin on the phenotype of breast cancer cells, Pathol. Oncol. Res., 2015, Vo. 21, No. 3, pp. 605-612.
Ling S., Tian Y., Zhang H., Jia K., Feng T., Sun D. et al. Metformin reverses multidrug resistance in human hepatocellular carcinoma Bel7402/5fluorouracil cells. Mol. Med. Rep., 2014, Vol. 10, No. 6, pp. 2891-2897.
Salani B., Del R.A., Marini C., Sambuceti G., Cordera R., Maggi D. Metformin, cancer and glucose metabolism, Endocr. Relat. Cancer, 2014, Vol. 21, No. 6, pp. R461-R471.
Fontaine E. Metformin and respiratory chain complex I: the last piece of the puzzle? Biochem. J., 2014, Vol. 463, No. 3, pp. e3-e5.
Troncone M., Cargnelli S. M., Villani L. A., Isfahanian N., Broadfield L. A., Zychla L. et al. Targeting metabolism and AMP-activated kinase with metformin to sensitize non-small cell lung cancer (NSCLC) to cytotoxic therapy; translational biology and rationale for current clinical trials, Oncotarget, 2017, Apr 27.
Marini C., Ravera S., Buschiazzo A., Bianchi G., Orengo A. M., Bruno S. et al. Discovery of a novel glucose metabolism in cancer: The role of endoplasmic reticulum beyond glycolysis and pentose phosphate shunt, Sci. Rep., 2016, No. 6, 25092.
Garbati P., Ravera S., Scarfi S., Salis A., Rosano C., Poggi A. et al. Effects on Energy Metabolism of Two Guanidine Molecules, (Boc) 2-Creatine and Metformin, J. Cell Biochem., 2017.
Zhao D., Long X. D., Lu T. F., Wang T., Zhang W. W., Liu Y. X. et al. Metformin decreases IL-22 secretion to suppress tumor growth in an orthotopic mouse model of hepatocellular carcinoma, Int. J. Cancer, 2015, Vol. 136, No. 11, pp. 2556-2565.
Cheng J., Huang T., Li Y., Guo Y., Zhu Y., Wang Q. et al. AMP-activated protein kinase suppresses the in vitro and in vivo proliferation of hepatocellular carcinoma, PLoS One, 2014, Vol. 9, No. 4, e93256.
Koh S. J., Kim J. M., Kim I. K., Ko S. H., Kim J. S. Anti-inflammatory mechanism of metformin and its effects in intestinal inflammation and colitis-associated colon cancer, J. Gastroenterol. Hepatol., 2014, Vol. 29, No. 3, pp. 502-510.

Еще

Статья научная