Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China.
Cancer Lett. 2011 Feb 28;301(2):212-20. doi: 10.1016/j.canlet.2010.12.004. Epub 2011 Jan 7.
We evaluated the efficacy of a combination strategy, Endostar, a modified recombinant human endostatin, plus dexamethasone, against angiogenesis and hepatoma growth. By colony formation assay, synergistic effects of the combination of Endostar and dexamethasone were observed on the proliferations of human umbilical endothelial cells and hepatoma Bel-7402 cells. Endostar plus dexamethasone inhibited angiogenesis events in vitro. Examined with transwell assay, HUVECs invasion was more efficiently suppressed by combination of Endostar and dexamethasone than by the respective single drug. But the combination treatment of Endostar and dexamethasone to Bel-7402 cells did not alter the migration of HUVECs. The migration of HUVEC tended to coincident with VEGF secretion as determined by ELISA. Tube formation assay, rat aortic ring assay and chick embryo chorioallantoic membrane (CAM) assay indicated that the anti-angiogenesis effects of Endostar were significantly enhanced by dexamethasone. In mouse hepatoma H22 and human hepatoma Bel-7402 subcutaneous xenograft, Endostar plus dexamethasone presented more potent efficacy in tumor growth suppression than the single drug treatments. The above confirms the synergism of Endostar and dexamethasone on anti-angiogenesis and suppression of hepatoma growth. The potentiation effects of the combination indicate that Endostar plus dexamethasone might be a positive strategy for cancer therapy.
我们评估了一种联合策略的疗效,即恩度(一种改良的重组人内皮抑素)联合地塞米松,针对血管生成和肝癌生长。通过集落形成实验,观察到恩度联合地塞米松对人脐静脉内皮细胞和肝癌 Bel-7402 细胞的增殖具有协同作用。恩度联合地塞米松抑制了体外血管生成事件。通过 Transwell 实验,与单独使用药物相比,恩度联合地塞米松更有效地抑制了 HUVEC 的侵袭。但恩度联合地塞米松对 Bel-7402 细胞的迁移没有改变。ELISA 检测结果表明,HUVEC 的迁移与 VEGF 的分泌趋势一致。管形成实验、大鼠主动脉环实验和鸡胚绒毛尿囊膜(CAM)实验表明,地塞米松显著增强了恩度的抗血管生成作用。在小鼠肝癌 H22 和人肝癌 Bel-7402 皮下移植瘤模型中,与单独用药相比,恩度联合地塞米松在肿瘤生长抑制方面表现出更强的疗效。以上结果证实了恩度和地塞米松在抗血管生成和抑制肝癌生长方面的协同作用。该联合的增效作用表明,恩度联合地塞米松可能是癌症治疗的一种积极策略。