Preparation and characterization of RGD tumour-homing-peptide-modified plasminogen K5
- 医学院－已发表论文 
Plasminogen K5 (kringle 5) has strong inhibitory effects on endothelial-cell proliferation and migration. It was reported that K5 can reduce tumour neovascularization, resulting in clinically relevant antitumour effects. To determine whether addition of a tumour targeting peptide could improve the tumour homing and antitumour activities of K5, we genetically modified K5 with an RGD (Arg-Gly-Asp) motif, which is a ligand with high affinity for alpha(v)beta(3) and alpha(v)beta(5) integrins. The fusion protein RGD K5 was expressed in the Pichia pastoris system and the biological activity of RGD K5 was assessed in vitro and in vivo. The results showed that the RGD-K5 exhibited a more potent effect of inhibiting endothelial cell proliferation and migration compared with that of traditional K5. RGD-K5 also displayed stronger anti-angiogenic activity in a CAM (chick chorioallantoic membrane) assay. Furthermore, RGD K5 also showed stronger anti-angiogenic and antitumour effects in BI6F10 melanoma-bearing mice compared with traditional K5. In conclusion, the biological activity of K5 can be further improved by the addition of a tumour-homing peptide, and the RGD K5 may prove to be a promising novel candidate for cancer therapy.