Urpilainen Elina, Puistola Ulla, Boussios Stergios, Karihtala Peeter
Department of Obstetrics and Gynaecology, PEDEGO Research Unit, Medical Research Center Oulu, University of Oulu and University Hospital of Oulu, Oulu, Finland.
Department of Medical Oncology, Medway NHS Foundation Trust, Gillingham, Kent, UK.
Ann Transl Med. 2020 Dec;8(24):1711. doi: 10.21037/atm-20-1060.
In recent decades, great interest in the off-label use of metformin has arisen as a result of its broad effects on different signaling pathways, with only a few side effects, and low cost. Metformin has been shown to have multiple, dose-dependent preclinical anticancer effects, which can be roughly divided into either direct effects via inhibition of mitochondrial respiratory chain complex I, or indirect effects through lowered glucose, insulin and insulin-like growth factor levels. Further details on and anticancer effects specifically in ovarian cancer are continuously reported. Preclinically metformin has clear chemosensitizing effects in ovarian cancer and it is an effective negative regulator of angiogenesis. There are also some epidemiological studies on metformin use in ovarian cancer, but the results of these studies are not as promising as those preclinical studies would indicate. Most preclinical studies have involved metformin concentrations that are many times higher than the pharmacological doses used in patients, which might confound the clinical use of metformin as regards the above-mentioned aspects. In this review we evaluate preclinical and clinical evidence concerning metformin in ovarian cancer treatment.
近几十年来，由于二甲双胍对不同信号通路具有广泛作用、副作用少且成本低，人们对其非标签用途产生了浓厚兴趣。二甲双胍已被证明具有多种剂量依赖性的临床前抗癌作用，大致可分为通过抑制线粒体呼吸链复合体I产生的直接作用，或通过降低葡萄糖、胰岛素和胰岛素样生长因子水平产生的间接作用。关于二甲双胍在卵巢癌中具体抗癌作用的更多细节不断被报道。临床前研究表明，二甲双胍在卵巢癌中具有明确的化学增敏作用，并且是血管生成的有效负调节剂。也有一些关于二甲双胍用于卵巢癌的流行病学研究，但其结果并不像临床前研究所显示的那样有前景。大多数临床前研究中使用的二甲双胍浓度比患者使用的药理剂量高出许多倍，这在上述方面可能会混淆二甲双胍的临床应用。在本综述中，我们评估了关于二甲双胍在卵巢癌治疗中的临床前和临床证据。
