[Metformin--new treatment strategies for gynecologic neoplasms].

二甲双胍 医学 PI3K/AKT/mTOR通路 子宫内膜癌 安普克 双胍 癌症 卵巢癌 癌症研究 内科学 西罗莫司 肿瘤科 信号转导 蛋白激酶A 激酶 胰岛素 生物 生物化学 细胞生物学
作者
Tomasz Milewicz,Марта Кялка,Sandra Mrozińska,Agnieszka Ociepka,J Krzysiek
出处
期刊:PubMed [National Institutes of Health]
卷期号:70 (2): 81-4 被引量:5
链接
摘要

Metformin, a drug from the biguanide class, is now one of the most widely used drugs in the treatment of type 2 diabetes. This drug was also used in the treatment of polycystic ovarian syndrome and recent reports indicate the possibility of using this drug in oncology. Latest findings show that metformin has an anticancer effect. Influencing the transduction mechanisms primarily through activation of protein kinase activated by 5'AMP (AMPK) regulates the activity of the AMPK/mTOR signaling pathway. MTOR pathway dysregulation may be a factor in the pathogenesis of various human diseases, especially cancers. Overactivation of mTOR is observed in malignant cells and is associated with their resistance to treatment. It can therefore be concluded that metformin as an inhibitor of mTOR may be a factor that suppresses tumor development. There are also studies showing that metformin prevents the formation of metastases, reducing tumor vasculature and improves the effectiveness of anticancer drugs. The anticancer effect of metformin has been proven in the treatment of colorectal and breast cancer. The current studies reports the positive effects in the treatment of gynecological cancers such as ovarian, endometrial and cervical cancer. Incidence for these tumors in 2009 in Poland was: for ovarian cancer 11.01100000; for endometrial cancer 15.0/100000; for cervical cancer 10.5/100000. Metformin has antitumor activity in monotherapy and also synergistically with other anticancer agents. Metformin has antiproliferative properties; reduces the VEGF levels, causing a reduction in tumor vasculature; causes an increase in progesterone receptor, which increases the response to hormonal therapy; inhibits the expression of glyoxalase I, mediating resistance to chemotherapy; decreases in the concentration of human telomerase; reduces the activity of Akt and Erk kinases, key regulators of metabolism and progression of tumors and also inhibits the formation of metastases.

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