期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 23, 期 10, 页码 7078-7087出版社
WILEY
DOI: 10.1111/jcmm.14610
关键词
acetylsalicylic acid; cell cycle; neuroblastoma; neuronal differentiation; Rb1
Several clinical and experimental studies have demonstrated that regular use of aspirin (acetylsalicylic acid, ASA) correlates with a reduced risk of cancer and that the drug exerts direct anti-tumour effects. We have previously reported that ASA inhibits proliferation of human glioblastoma multiforme-derived cancer stem cells. In the present study, we analysed the effects of ASA on nervous system-derived cancer cells, using the SK-N-SH (N) human neuroblastoma cell line as an experimental model. ASA treatment of SK-N-SH (N) dramatically reduced cell proliferation and motility, and induced neuronal-like differentiation, indicated by the appearance of the neuronal differentiation marker tyrosine hydroxylase (TH) after 5 days. ASA did not affect cell viability, but caused a time-dependent accumulation of cells in the G(0)/G(1) phase of the cell cycle, with a concomitant decrease in the percentage of cells in the G(2) phase. These effects appear to be mediated by a COX-independent mechanism involving an increase in p21(Waf1) and underphosphorylated retinoblastoma (hypo-pRb1) protein levels. These findings may support a potential role of ASA as adjunctive therapeutic agent in the clinical management of neuroblastoma.
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