Notch信号通路对血管生成的影响及中医药作用的研究进展

Notch信号通路是一条在结构上进化保守的信号转导系统,为正常胚胎发育、组织稳态调控以及成体组织中的干细胞维持所必需的,并调控许多细胞生物过程。已有研究证实,异常表达的Notch信号参与肿瘤的血管生成,而且Notch的配体Dll4在肿瘤血管生成过程中起到一个负反馈的调节作用。常规抗肿瘤血管生成的治疗策略主要是阻止促血管生成因子刺激内皮细胞(如抗VEGF治疗),但阻断Dll4-Notch信号通路可显著增加肿瘤血管的生成,其作用可能是通过促进功能缺陷血管的过多生成而抑制肿瘤生长。虽然Dll4-Notch信号通路的靶向治疗还处在早期阶段,但已成为临床抗肿瘤治疗的新靶点,并且为中医药抗肿瘤血管生成的研究提供了新的方向。

Research Progress on Effects of Notch Signaling Pathway on Tumor Angiogenesis and Action of Chinese Medicine

Notch signaling pathway is a highly conserved signaling system that is essential for normal embryonic development, tissue homeostasis and stem cell maintenance in adult tissues and regulates many cellular biological processes. It has been demonstrate that aberrant Notch signaling is implicated in tumor angiogenesis, and the Notch ligand Dll4 functions as a negative regulator of tumor angiogenesis. Conventional angiogenesis-based treatments of tumors, for example, anti-VEGF therapy, have focused on preventing pro-angiogenic factor from stimulating endothelial cells. Blockade of Dll4-Notch in tumors results in excessive hut non-productive angiogenesis which restrains tumor growth. Although the development of Dll4 inhibitors are still in the early stages, it has been a promising new therapeutic target in clinical practice and may provide a new direction for the research of Chinese medicine in inhibiting tumor angiogenesis.