Department of Pharmacology, Pennsylvania State University College of Medicine, Hershey, 17033, USA.
Anticancer Agents Med Chem. 2011 Nov;11(9):911-9. doi: 10.2174/187152011797655177.
The bioactive sphingolipid, ceramide, has garnered major interest as a principle regulator of cellular stress, proliferation, senescence, and death. Of particular interest to cancer biologists and clinical oncologist, dysregulated ceramide metabolism has been documented in both solid and non-solid malignancies. Moreover, most anticancer chemotherapeutics stimulate ceramide accumulation through increased ceramide synthesis or through the inhibition of ceramide catabolism. In fact, neutralization of ceramide via glycosylation or phosphorylation in malignant cells has been linked to multidrug chemoresistance. New therapeutic strategies to overcome chemoresistance focus on increasing endogenous ceramide levels by stimulating ceramide synthesis, by inhibiting ceramide neutralization, or by the direct delivery of exogenous ceramide. This review will discuss new therapeutic strategies designed specifically to modulate ceramide metabolism, as well as nanoscale delivery systems engineered to selectively deliver ceramide to cancerous cells and tissues.
生物活性神经酰胺作为细胞应激、增殖、衰老和死亡的主要调节因子，引起了广泛关注。癌症生物学家和临床肿瘤学家特别感兴趣的是，在实体瘤和非实体瘤中都发现了失调的神经酰胺代谢。此外，大多数抗癌化疗药物通过增加神经酰胺合成或抑制神经酰胺分解代谢来刺激神经酰胺积累。事实上，通过糖基化或磷酸化使恶性细胞中的神经酰胺失活已与多药耐药性相关。克服化疗耐药性的新治疗策略侧重于通过刺激神经酰胺合成、抑制神经酰胺中和或直接递送来增加内源性神经酰胺水平。本文综述了专门用于调节神经酰胺代谢的新治疗策略，以及为选择性将神经酰胺递送到癌细胞和组织而设计的纳米级递药系统。
