Department of Experimental Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
PLoS One. 2013 Mar 5;8(3):e58723. doi: 10.1371/journal.pone.0058723. Print 2013.
Endoglin is a transforming growth factor-β (TGF- β) co-receptor that participates in the activation of a signaling pathway that mediates endothelial cell proliferation and migration in angiogenic tumor vasculature. Therefore, silencing of endoglin expression is an attractive approach for antiangiogenic therapy of tumors. The aim of our study was to evaluate the therapeutic potential of small interfering RNA (siRNA) molecules against endoglin in vitro and in vivo. Therapeutic potential in vitro was assessed in human and murine endothelial cells (HMEC-1, 2H11) by determining endoglin expression level, cell proliferation and tube formation. In vivo, the therapeutic potential of siRNA molecules was evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice. Results of our study showed that siRNA molecules against endoglin have a good antiangiogenic therapeutic potential in vitro, as expression of endoglin mRNA and protein levels in mouse and human microvascular endothelial cells after lipofection were efficiently reduced, which resulted in the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransfer of siRNA molecules into TS/A mammary adenocarcinoma also significantly reduced the mRNA levels, number of tumor blood vessels and the growth of tumors. The obtained results demonstrate that silencing of endoglin is a promising antiangiogenic therapy of tumors that could not be used as single treatment, but as an adjunct to the established cytotoxic treatment approaches.
内皮糖蛋白是转化生长因子-β（TGF-β）的共受体，参与介导血管生成肿瘤血管内皮细胞增殖和迁移的信号通路的激活。因此，沉默内皮糖蛋白的表达是肿瘤抗血管生成治疗的一种有吸引力的方法。我们的研究目的是评估针对内皮糖蛋白的小干扰 RNA（siRNA）分子在体外和体内的治疗潜力。通过测定内皮糖蛋白表达水平、细胞增殖和管形成，在人源和鼠源内皮细胞（HMEC-1、2H11）中评估体外治疗潜力。在生长于 BALB/c 小鼠的 TS/A 乳腺腺癌中评估体内 siRNA 分子的治疗潜力。我们的研究结果表明，针对内皮糖蛋白的 siRNA 分子在体外具有良好的抗血管生成治疗潜力，因为脂质体转染后鼠源和人源微血管内皮细胞中内皮糖蛋白 mRNA 和蛋白水平的表达被有效降低，导致内皮细胞增殖和管形成受到抑制。在体内，通过三重电转移将 siRNA 分子转染到 TS/A 乳腺腺癌中也能显著降低肿瘤血管的 mRNA 水平、数量和肿瘤生长。这些结果表明，沉默内皮糖蛋白是一种很有前途的肿瘤抗血管生成治疗方法，不能作为单一治疗方法，但可以作为已建立的细胞毒性治疗方法的辅助手段。
