Milewicz Tomasz, Kiałka Marta, Mrozińska Sandra, Ociepka Agnieszka, Krzysiek Józef
Klinika Endokrynologii Ginekologicznej, Uniwersytet Jagielloński, Collegium Medicum, Kraków.
Przegl Lek. 2013;70(2):81-4.
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.
二甲双胍是一种双胍类药物，目前是治疗2型糖尿病最广泛使用的药物之一。该药物也曾用于治疗多囊卵巢综合征，最近的报告表明其在肿瘤学领域有应用的可能性。最新研究结果显示，二甲双胍具有抗癌作用。它主要通过激活5'-单磷酸腺苷激活的蛋白激酶（AMPK）来影响转导机制，从而调节AMPK/mTOR信号通路的活性。mTOR通路失调可能是多种人类疾病，尤其是癌症发病机制中的一个因素。在恶性细胞中观察到mTOR过度激活，且这与它们的治疗耐药性有关。因此可以得出结论，二甲双胍作为mTOR的抑制剂可能是抑制肿瘤发展的一个因素。也有研究表明，二甲双胍可防止转移形成，减少肿瘤血管生成，并提高抗癌药物的疗效。二甲双胍的抗癌作用已在结直肠癌和乳腺癌的治疗中得到证实。目前的研究报道了其在卵巢癌、子宫内膜癌和宫颈癌等妇科癌症治疗中的积极效果。2009年波兰这些肿瘤的发病率分别为：卵巢癌11.0/100000；子宫内膜癌15.0/100000；宫颈癌10.5/100000。二甲双胍在单一疗法中具有抗肿瘤活性，并且与其他抗癌药物具有协同作用。二甲双胍具有抗增殖特性；降低血管内皮生长因子（VEGF）水平，导致肿瘤血管生成减少；使孕激素受体增加，从而增强对激素治疗的反应；抑制乙二醛酶I的表达，介导对化疗的耐药性；降低人端粒酶的浓度；降低Akt和Erk激酶的活性，这两种激酶是肿瘤代谢和进展的关键调节因子，并且还抑制转移的形成。
