Lung Cancer. 2011 Jan;71(1):113-5. doi: 10.1016/j.lungcan.2010.10.016. Epub 2010 Nov 20.
The drug-dependent induction of premature senescence in neoplastic cells is considered per se an important tumor suppressive mechanism. DNA demethylating agents recently introduced in clinical trials, such as 5-aza-cytidine (Decitabine) and its derivatives, have been extensively characterized in recent years as antiproliferative compounds that act through multiple mechanisms, which have not yet been fully clarified. We recently analyzed the introduction of Decitabine in therapy for malignant pleural mesothelioma (MPM) observing that, despite the ability to induce profound biological effects in MPM cells, the drug failed to generate a massive apoptotic response. Since one of the most intriguing aspects of DNA demethylating agents is the possibility to accelerate the senescent response of tumor cells, we investigated the hypothesis of Decitabine inducing, in vitro, the premature aging of MPM cells.
肿瘤细胞中药物依赖性的衰老诱导被认为是一种重要的肿瘤抑制机制。近年来，在临床试验中引入的 DNA 去甲基化剂，如 5-氮杂胞苷（地西他滨）及其衍生物，已被广泛研究为具有多种作用机制的抗增殖化合物，这些机制尚未完全阐明。我们最近分析了地西他滨在恶性胸膜间皮瘤（MPM）治疗中的应用，观察到尽管地西他滨能够在 MPM 细胞中诱导深刻的生物学效应，但该药物未能引发大量的细胞凋亡反应。由于 DNA 去甲基化剂最引人注目的方面之一是有可能加速肿瘤细胞的衰老反应，我们研究了地西他滨在体外诱导 MPM 细胞过早衰老的假说。
