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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 is the third generation of bisphosphonate drugs, mainly used for the treatment of malignant hypercalcemia and bone metastases. The current study found that in addition to inhibiting the absorption of zoledronic acid also has direct and indirect anti-tumor activity. Among them, the inhibition of tumor angiogenesis is one of the mechanisms of its indirect anti-tumor effect. The anti-angiogenic effect may be as follows: (1) inhibit the secretion of VEGF from tumor cells and tumor stromal cells and regulate the autocrine loop of VEGF-VEGFR to inhibit angiogenesis; (2) inhibit the migration and adhesion of vascular endothelial cells; (3) Induce apoptosis of circulating progenitor cells of endothelial cells and inhibit the secretion of MMPs by tumor cells and tumor-infiltrating macrophages; (4) Inhibit angiogenic mimicry of tumor cells. However, the dose of zoledronic acid antitumor activity is different from the current dose of bone metastasis treatment, and its anti-tumor angiogenic mimicry mechanism is not yet clear and needs further study.