Malignant pleural mesothelioma (MPM) is an aggressive asbestos-related cancer arising from the mesothelial cells lining the pleural cavity. MPM is characterized by a silent clinical progression and a highly resistance to conventional chemo/radio-therapies. MPM patients die in a few months/years from diagnosis. Notch signaling is a well-conserved cell communication system, which regulates many biological processes. In humans, the dysregulation of Notch pathway potentially contributes to cancer onset/progression, including MPM. Metformin is the first-line drug used to treat type 2 diabetes mellitus. Metformin is proven to be an effective antitumor drug in preclinical models of different types of cancer. To date, clinical efficacy is being studied in many clinical trials. In this study, the anti-proliferative effect of metformin on MPM cells and the putative involvement of Notch1 as a mediator of metformin activities, were investigated. MPM cells showed high levels of Notch1 activation compared to normal pleural mesothelial cells. Furthermore, metformin treatment hampered MPM cell proliferation and enhanced the apoptotic process, accompanied by decreased Notch1 activation.

恶性胸膜间皮瘤（MPM）是一种侵袭性石棉相关的癌症，由胸膜腔内的间皮细胞引起。MPM的特点是无声的临床进展和对常规化学/放射疗法的高度耐药性。MPM患者自诊断后数月/数年内死亡。陷波信号传导是保存良好的细胞通信系统，其调节许多生物学过程。在人类中，Notch通路的失调可能导致癌症的发生/发展，包括MPM。二甲双胍是用于治疗2型糖尿病的一线药物。在不同类型癌症的临床前模型中，二甲双胍被证明是一种有效的抗肿瘤药物。迄今为止，许多临床试验正在研究临床疗效。在这个研究中，研究了二甲双胍对MPM细胞的抗增殖作用以及Notch1作为二甲双胍活性介质的假定参与。与正常的胸膜间皮细胞相比，MPM细胞显示出高水平的Notch1激活。此外，二甲双胍治疗阻碍了MPM细胞的增殖并增强了凋亡过程，并伴有Notch1激活减少。