20.500.12556/RUP-7057 Endoglin (CD105) silencing mediated by shRNA under the control of Endothelin-1 promoter for targeted gene therapy of Melanoma Endoglin (CD105), a transforming growth factor (TGF)-% coreceptor, and endothelin-1, a vasoconstrictor peptide, are both overexpressed in tumor endothelial and melanoma cells. Their targeting is therefore a promising therapeutic approach for melanoma tumors. The aim of our study was to construct a eukaryotic expression plasmid encoding the shRNA molecules against CD105 under the control of endothelin-1 promoter and to evaluate its therapeutic potential both in vitro in murine B16F10-luc melanoma and SVEC4-10 endothelial cells and in vivo in mice bearing highly metastatic B16F10-luc tumors. Plasmid encoding shRNA against CD105 under the control of the constitutive U6 promoter was used as a control. We demonstrated the antiproliferative and antiangiogenic effects of both plasmids in SVEC4-10 cells, as well as a moderate antitumor and pronounced antimetastatic effect in B16F10-luc tumors in vivo. Our results provide evidence that targeting melanoma with shRNA molecules against CD105 under the control of endothelin-1 promoter is a feasible and effective treatment, especially for the reduction of metastatic spread. melanoma electroporation endoglin (CD105) endothelin-1 gene therapy true false false Angleški jezik Neznan jezik Delo ni kategorizirano 2015-10-14 06:26:38 2015-10-14 06:26:38 2024-03-01 12:51:13 0000-00-00 00:00:00 2015 0 0 No. 4 May 2015 0000-00-00 NiDoloceno NiDoloceno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 2162-2531 577.2 1898619 10.1038/mtna.2015.12 1537399748 http://www.nature.com/mtna/journal/v4/n5/full/mtna201512a.html 1 https://repozitorij.upr.si/Dokument.php?lang=slv&id=7057 Fakulteta za vede o zdravju 0 0 0