论文部分内容阅读
在许多肿瘤的发生发展过程中,鞘磷脂的代谢产物神经酰胺(ceramide,Cer)、神经鞘氨醇(sphingosine,Sph)和1-磷酸鞘氨醇(sphingosine-1-phosphate,S1P)发挥着极为重要的作用,它们调节着细胞的增殖、存活和凋亡。在细胞内,这些代谢产物可以相互转化,鞘氨醇激酶(sphingosine kinase,SphK)则是维系Cer、Sph和S1P三者间代谢平衡的关键酶,具有调节Cer和S1P的双重功能。SphK在多种实体肿瘤中均有表达,其基因具有癌基因的特征,并且通过Sphk/S1P信号途径对肿瘤发挥着促进细胞生长,保护其免受凋亡,使肿瘤细胞产生放化疗耐受的作用。而Sphk抑制剂的应用实现了其活性的下调,阻滞了其在恶性肿瘤中的作用。因此,Sphk的靶向肿瘤治疗有可能实现对肿瘤更为有效的控制,具有良好的应用前景。
In many tumors, sphingosine-1-phosphate (S1P), a metabolite of sphingomyelin, plays a very important role Important role, they regulate cell proliferation, survival and apoptosis. In the cell, these metabolites can be transformed into each other. SphK is a key enzyme that maintains the metabolic balance between Cer, Sph and S1P, and regulates the dual functions of Cer and S1P. SphK is expressed in a variety of solid tumors, and its genes are characterized by oncogenes. SphK plays an important role in cancer growth through Sphk / S1P signal pathway, which protects the tumor from apoptosis and makes the tumor cells resistant to radiotherapy and chemotherapy effect. The application of Sphk inhibitors to achieve its activity down, blocking its role in cancer. Therefore, Sphk’s targeted tumor therapy is likely to achieve more effective tumor control and has good application prospects.