The role of metformin in the treatment of hematological diseases

سال انتشار: 1398
نوع سند: مقاله کنفرانسی
زبان: انگلیسی
مشاهده: 342

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شناسه ملی سند علمی:

HUMS01_069

تاریخ نمایه سازی: 6 اسفند 1398

چکیده مقاله:

Background and Objective: Metformin is a member of the Biguanide class and is one of the most widely used anti-hyperglycemic drugs for the treatment of type 2 diabetes. In addition, the use of metformin in the treatment of various diseases including polycystic ovary syndrome, antipsychotic induced weight gain and various cancers has been proven. In vitro studies showed that metformin can inhibit cancer cell proliferation in a variety of solid tumor cell lines including prostate, colorectal, lung, pancreatic, and breast. The anti-cancer effects of metformin are associated with direct (insulinindependent) and indirect (insulin-dependent) actions of this drug. In direct pathway, Metformin activates AMPK and inhibit mTOR cascade, and also this drug can indirectly inhibit mTOR by decreasing activation of insulin receptor/IGF-1 receptor and Akt. These functions lead to increased levels of autophagy, apoptosis, cell cycle arrest, decreased cell proliferation, migration, and invasion. Since this drug has a few side effects and is approved by the Food and Drug Administration (FDA), its role in the treatment of hematological diseases have investigated. Search Method: The resource of this study are from various sites and journals such as Google Scholar PubMed, Web of science, Hematologica, Blood, Nature. Objective: The aim of this study was to investigate the role of metformin in the treatment of hematological diseases. Results: Studies have shown that metformin is effective in the treatment of some hematological diseases. In anemia, this drug reduces the risk of vaso-occlusive crisis in patients with sickle cell anemia and increases hemoglobin F through activation of FOXO3 to improve the symptoms of hese patients and patients with thalassemia. Also in a mice model of Fanconi anemia, Metformin improves hematopoiesis, delays in tumor formation and reduces damage of DNA. Several studies have demonstrated that metformin has anti-leukemic properties. In acute promyelocytic leukemia, combination treatment of metformin with trans-retinoic acid is related to differentiation and apoptosis of leukemic blasts. In addition, this drug inhibits cell growth and induces apoptosis in ALL cells through AMPK-dependent pathway and improves survival of patients. Also Metformin exerts anti-leukemia activity in JAK2V617Fpositive myeloproliferative neoplasms and reduced cell viability, cell proliferation, clonogenicity, and delayed cell cycle progression in this cells. CLL cells that are sensitive to the dasatinib appears to be killed by metformin. Cytostatic effect of metformin was accompanied by decreased expression of survival and proliferation-associated proteins, inhibition of signaling pathways involved in CLL disease progression and decreased intracellular glucose available for glycolysis. Studies show that combination treatment of metformin and dexamethasone causes myeloma cell death through inhibition of AKT / mTOR signaling pathway. It also reduced IL-6R expression through AMPK, mTOR and miR34a pathways and subsequently decreased myeloma cell growth and survival. Conclusion: Studies identify metformin as a potential therapeutic agent for hematologic disease. Also the combined use of metformin with chemotherapy is effective in some hematological disease.

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نویسندگان

Maedeh Alipour

Master of Hematology, Shiraz University of Medical Sciences, Shiraz, Iran

Samira Nafar

Master of Human genetic, Shiraz University of Medical Sciences, Shiraz, Iran