血小板型12-脂加氧酶与肿瘤

花生四烯酸通过脂加氧酶(lipoxygenase,LOX)途径代谢产生多种生物活性脂类,这些脂类在炎症、血栓形成和肿瘤演进过程中发挥着重要的作用。LOX按照组织分布被分为5- 、8- 、12 -、15- LOX4 个家族,血小板型12 LOX是LOX的一种,催化花生四烯酸转化为廿碳四烯酸。血小板型12 -LOX在正常组织中主要分布在血小板、人皮肤表皮细胞细胞质和微粒体中。近来研究发现,在多种肿瘤组织和肿瘤细胞系中不仅可检测到血小板型12- LOX的表达,且随着肿瘤级别的增高,瘤细胞表达增强。血小板型12 -LOX催化的代谢产物,如12(S) 羟廿碳四烯酸,已被证明涉及肿瘤细胞凋亡、肿瘤血管形成,因此血小板型12 LOX也成为肿瘤治疗的潜在目标。多项研究表明,血小板型12 -LOX的抑制剂能有效抑制肿瘤,如去甲二氢愈创木酸能有效抑制胶质瘤。对血小板型12- LOX与肿瘤细胞增殖、凋亡和血管生成之间的关系以及其机制进行讨论,另外,对血小板型12- LOX抑制剂预防和治疗肿瘤予以综述。

Platelet-type 12-lipoxygenase and Tumor

Arachidonic acid metabolism through lipoxygenase (LOX)pathways generates various biologically active lipids that play important roles in inflammation, thrombosis and tumor progression. The family of LOXs is divided into four subtypes according to tissue distribution; 5-, 8-, 12-, and 15-LOX. Platelet-type 12-LOX catalyzes the conversion of arachidonic acid to 12-hydroxyeicosatetraenoic (12-HETE).Platelet-type 12-LOX is predominatly expressed in platelet, microsome and cytoplasm of human skin epithelial cell.In recent research, platelet-type 12-LOX expression was found in many tumor tissues and cell lines. The expression increased in a grade-dependent manner.Platelet-type 12-LOX metabolites, such as 12(s)-HETE, have been found to involve in the regulation of apoptosis, angiogensis of tumor. Multiple studies have shown that platelet-type 12-LOX inhibitors effectively prevent many tumors, such as NDGA can effectively prevent experimental glioma.In this review, the association between platelet-type 12-LOX and tumor cell apoptosis, angiogensis and potential mechanisms of this effect are discussed. Additionally, evidence supporting the role of platelet -type 12-LOX inhibitors for the prevention and treatment of tumor is reviewed.