Sietsma Hannie, Dijkhuis Anne Jan, Kamps Willem, Kok Jan Willem
Department of Pathology and Laboratory Medicine, University Hospital Groningen, The Netherlands.
Neurochem Res. 2002 Aug;27(7-8):665-74. doi: 10.1023/a:1020228117739.
Disseminated neuroblastoma usually calls for chemotherapy as the primary approach for treatment. Treatment failure is often attributable to drug resistance. This involves a variety of cellular mechanisms, including increased drug efflux through expression of ATP-binding cassette transporters (e.g., P-glycoprotein) and the inability of tumor cells to activate or propagate the apoptotic response. In recent years it has become apparent that sphingolipid metabolism and the generation of sphingolipid species, such as ceramide, also play a role in drug resistance. This may involve an autonomous mechanism, related to direct effects of sphingolipids on the apoptotic response, but also a subtle interplay between sphingolipids and ATP-binding cassette transporters. Here, we present an overview of the current understanding of the multiple levels at which sphingolipids function in drug resistance, with an emphasis on sphingolipid function in neuroblastoma and how modulation of sphingolipid metabolism may be used as a novel treatment paradigm.
播散性神经母细胞瘤通常需要以化疗作为主要治疗方法。治疗失败往往归因于耐药性。这涉及多种细胞机制，包括通过ATP结合盒转运蛋白（如P-糖蛋白）的表达增加药物外排，以及肿瘤细胞无法激活或启动凋亡反应。近年来，很明显鞘脂代谢和鞘脂类物质（如神经酰胺）的生成在耐药性中也起作用。这可能涉及一种自主机制，与鞘脂对凋亡反应的直接作用有关，但也涉及鞘脂与ATP结合盒转运蛋白之间的微妙相互作用。在此，我们概述了目前对鞘脂在耐药性中发挥作用的多个层面的理解，重点是鞘脂在神经母细胞瘤中的功能，以及如何调节鞘脂代谢可作为一种新的治疗模式。
