Pozzoli Giacomo, Marei Hany E, Althani Asma, Boninsegna Alma, Casalbore Patrizia, Marlier Lionel N J L, Lanzilli Giulia, Zonfrillo Manuela, Petrucci Giovanna, Rocca Bianca, Navarra Pierluigi, Sgambato Alessandro, Cenciarelli Carlo
Institute of Pharmacology, Università Cattolica del Sacro Cuore, Rome, Italy.
Pharmacology Unit, Fondazione Policlinico A. Gemelli IRCCS, Rome, Italy.
J Cell Physiol. 2019 Sep;234(9):15459-15471. doi: 10.1002/jcp.28194. Epub 2019 Jan 30.
Several clinical studies indicated that the daily use of aspirin or acetylsalicylic acid reduces the cancer risk via cyclooxygenases (Cox-1 and Cox-2) inhibition. In addition, aspirin-induced Cox-dependent and -independent antitumor effects have also been described. Here we report, for the first time, that aspirin treatment of human glioblastoma cancer (GBM) stem cells, a small population responsible for tumor progression and recurrence, is associated with reduced cell proliferation and motility. Aspirin did not interfere with cell viability but induced cell-cycle arrest. Exogenous prostaglandin E significantly increased cell proliferation but did not abrogate the aspirin-mediated growth inhibition, suggesting a Cox-independent mechanism. These effects appear to be mediated by the increase of p21 and p27 , associated with a reduction of Cyclin D1 and Rb1 protein phosphorylation, and involve the downregulation of key molecules responsible for tumor development, that is, Notch1, Sox2, Stat3, and Survivin. Our results support a possible role of aspirin as adjunctive therapy in the clinical management of GBM patients.
多项临床研究表明，每日服用阿司匹林或乙酰水杨酸可通过抑制环氧化酶（Cox-1和Cox-2）降低癌症风险。此外，阿司匹林诱导的Cox依赖性和非依赖性抗肿瘤作用也已得到描述。在此，我们首次报告，用阿司匹林处理人类胶质母细胞瘤（GBM）干细胞（一小部分导致肿瘤进展和复发的细胞），会使细胞增殖和运动能力降低。阿司匹林不影响细胞活力，但会诱导细胞周期停滞。外源性前列腺素E显著增加细胞增殖，但并未消除阿司匹林介导的生长抑制作用，提示存在一种不依赖Cox的机制。这些作用似乎是由p21和p27的增加介导的，这与细胞周期蛋白D1和Rb1蛋白磷酸化的减少有关，并且涉及对肿瘤发展起关键作用的分子（即Notch1、Sox2、Stat3和Survivin）的下调。我们的结果支持阿司匹林在GBM患者临床管理中作为辅助治疗的潜在作用。
