唑来膦酸抗肿瘤血管生成作用研究进展

Progress of Zoledronic Acid on Antiangiogenesis Effects

唑来膦酸是第三代双膦酸盐药物,主要用于治疗恶性高钙血症及骨转移癌。目前的研究发现,除抑制骨吸收外唑来膦酸还具有直接和间接的抗肿瘤活性。其中抑制肿瘤血管形成是其间接抗肿瘤作用机制之一。其抗肿瘤血管生成作用可能机制如下:(1)抑制肿瘤细胞及肿瘤间质细胞分泌VEGF,调节VEGF-VEGFR自分泌环抑制血管生成;(2)抑制血管内皮细胞迁移、黏附作用;(3)诱导循环内皮细胞祖细胞凋亡,抑制肿瘤细胞及肿瘤浸润巨噬细胞分泌MMPs;(4)抑制肿瘤细胞血管生成拟态。但唑来膦酸抗肿瘤活性的用药剂量不同于目前治疗骨转移的剂量,其抗肿瘤血管生成拟态的作用机制尚未明确,需要进一步研究。

Zoledronic acid belongs to the third generation of diphosphonate and mainly be applied for treatment of malignant hypercalcinemia and bone metastasis. Except inhibiting bone resorption, it also has direct and indirect antitumor activities. Antiangiogenesis effect is one kind of its indirect antitumor activities, by inhibiting the secretion of VEGF from tumor cells and mesenchyma cells to regulate VEGF-VEGFR endocrine cycle, depressing migration and adhesion of endothelial cells, inducing apoptosis of endothelial progenitor cells, inhibiting the secretion of MMPs from tumor cells and tumor-associated macrophages(TAM) and inhibiting vasculogenic mimicry of tumor cells. However, the dose of Zoledronic acid used for antineoplastic activity is different from that for bone metastasis. How it can inhibit vasculogenic mimicry is still needed further research.