血管内皮生长因子A在宫颈癌发病机制中的研究进展

Research Progress of Vascular Endothelial Growth Factor-A in the Pathogenesis of Cervical Cancer

血管内皮生长因子A(VEGF-A)是促进血管形成的特异性调节因子。在宫颈病变及宫颈癌的恶性转化中,VEGF-A通过诱导肿瘤血管生成为肿瘤细胞提供营养物质和转移途径。在VEGF-A活化的血管生成通路中,各类关键分子参与宫颈癌的发生发展,其中人乳头瘤病毒(HPV)感染产生的E6、E7蛋白及激活免疫模式识别受体和调节细胞脂肪酸代谢的过氧化物酶增殖体激活受体(PPARs)等均参与VEGF-A上游信号通路的调控,而且多种微小RNA(mi RNA)也参与VEGF-A转录后及下游信号通路的调控。VEGF-A与VEGF受体2(VEGFR-2)结合激活下游信号通路,通过促进内皮细胞增殖、存活、迁移和增加血管通透性等诱导宫颈癌血管生成。此外VEGF-A还能激活Delta样配体(DLL)/Notch信号通路,其在内皮细胞分化过程中发挥关键作用。综述VEGF-A的结构和功能及其相关的信号通路分子在宫颈癌发病机制及靶向治疗的研究,为明确宫颈癌的发病机制、寻找治疗靶点提供新思路。

Vascular endothelial growth factor-A （VEGF-A） is a specific regulator of angiogenesis. In the transition from cervical lesions to cervical cancer, VEGF-A provides tumor cells with nutrients and transfer pathways by inducing angiogenesis. A variety of molecules that play a crucial role in VEGF-A activated angiogenesis signaling pathways participate in the development of cervical cancer. E6, E7 proteins and immune Toll-like receptors induced by HPV infection and peroxisome proliferator-activated receptors （PPARs） that have been reported to regulate the cellular fatty acid metabolism participate in the regulation of VEGF-A upstream signaling pathway. A variety of micoRNAs are also involved in the regulation of VEGF-A post-transcription and downstream signaling pathways, then induces angiogenesis in cervical cancer by promoting endothelial cell proliferation, survival, migration, and increasing vascular permeability. In addition, VEGF-A also can activate the DLL/Notch signaling pathway, which plays a key role in the process of endothelial cell differentiation. This article will do a review in the structure and function of VEGF-A and its related signal pathways in the pathogenesis of cervical carcinoma and targeted therapy, which may provide new ideas for analysing the pathogenesis of cervical cancer and searching for its therapeutic targets.