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首页> 外文期刊>Cancer biology & therapy >Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid
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Evaluation of the in vitro and in vivo antiangiogenic effects of denosumab and zoledronic acid

机译：评价地诺单抗和唑来膦酸的体外和体内抗血管生成作用

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Denosumab (Dmab) and zoledronic acid (ZOL) are antiresorptive agents, with different mechanisms of action, that are indicated for delaying the onset of skeletal-related events in patients with bone metastases from solid tumors. Clinical and preclinical data suggest that ZOL may have also anti-angiogenic activity; however, the effects of Dmab (a fully humanized antibody against the receptor activator of nuclear factor kappa B ligand) on angiogenesis are largely unknown. The objective of this study was to compare the potential anti-angiogenic activity of Dmab with that of ZOL in preclinical models. Dmab (0.31 to 160 μM) had no effect on the viability of human MDA-MB-436 and CG5 breast cancer cells or human umbilical vein endothelial cells (HUVECs) and no effect on tubule formation or invasion of HUVECs. In contrast, ZOL (0.31 to 160 μM) decreased the viability of breast cancer and HUVECs in a time- and concentration-dependent manner and also inhibited HUVEC tubule formation and invasion. In vivo, ZOL (20 μg/mouse three times a week for three consecutive weeks) inhibited angiogenesis in Matrigel plugs and inhibited the growth and neo-angiogenesis of CG5 xenografts in athymic nude mice. In contrast, Dmab (10 mg/kg twice a week for four consecutive weeks) had no effect on Matrigel vascularization or xenograft growth in this model. These findings support the potential antiangiogenic and anticancer activity of ZOL in vitro and in vivo and further suggest that Dmab does not have antiangiogenic activity. Additional studies are needed to elucidate the potential anticancer activity of Dmab.
机译：Denosumab（Dmab）和zoledronic acid（ZOL）是具有不同作用机制的抗再吸收剂，适用于延缓实体瘤骨转移患者骨骼相关事件的发作。临床和临床前数据表明ZOL可能还具有抗血管生成活性。然而，Dmab（针对核因子κB配体的受体活化剂的完全人源化抗体）对血管生成的作用尚不清楚。这项研究的目的是在临床前模型中比较Dmab和ZOL的潜在抗血管生成活性。 Dmab（0.31至160μM）对人MDA-MB-436和CG5乳腺癌细胞或人脐静脉内皮细胞（HUVEC）的生存力没有影响，对肾小管的形成或HUVEC的入侵也没有影响。相反，ZOL（0.31至160μM）以时间和浓度依赖性方式降低了乳腺癌和HUVEC的生存力，还抑制了HUVEC小管的形成和侵袭。在体内，ZOL（20μg/小鼠，连续三周每周三次，每周三次）抑制了无胸腺裸鼠中Matrigel栓塞中的血管生成，并抑制了CG5异种移植物的生长和新血管生成。相反，在该模型中，Dmab（10 mg / kg每周两次，连续四周）对基质胶的血管形成或异种移植物生长没有影响。这些发现支持ZOL在体外和体内的潜在抗血管生成和抗癌活性，并且进一步表明Dmab不具有抗血管生成活性。需要进一步的研究来阐明Dmab的潜在抗癌活性。

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