Multiple Delivery of siRNA against Endoglin into Murine Mammary Adenocarcinoma Prevents Angiogenesis and Delays Tumor Growth

Abstract

Endoglin is a transforming growth factor-β (TGF- β)co-receptor that participates in the activation of a signaling pathwaythat mediates endothelial cell proliferation and migration in angiogenic tumorvasculature. Therefore, silencing of endoglin expression is an attractiveapproach for antiangiogenic therapy of tumors. The aim of our study was toevaluate the therapeutic potential of small interfering RNA (siRNA)molecules against endoglin in vitro and invivo. Therapeutic potential in vitro wasassessed 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 moleculeswas evaluated in TS/A mammary adenocarcinoma growing in BALB/c mice.Results of our study showed that siRNA molecules against endoglin have a goodantiangiogenic therapeutic potential in vitro,as expression of endoglin mRNA and protein levels in mouse and human microvascularendothelial cells after lipofection were efficiently reduced, which resultedin the inhibition of endothelial cell proliferation and tube formation. In vivo, silencing of endoglin with triple electrotransferof siRNA molecules into TS/A mammary adenocarcinoma also significantlyreduced the mRNA levels, number of tumor blood vessels and the growth of tumors.The obtained results demonstrate that silencing of endoglin is a promisingantiangiogenic therapy of tumors that could not be used as single treatment,but as an adjunct to the established cytotoxic treatment approaches. © 2013 Dolinsek et al.