Vascular basement membrane-derived multifunctional peptide, a novel inhibitor of angiogenesis and tumor growth

Vascular basement membrane-derived multifunctional peptide(VBMDMP)gene(fusion gene of the human immunoglobulin G3 upper hinge region and two tumstatin-derived fragments)obtained by chemical synthesis was cloned into vector pUC19,and introduced into the expression vector pGEX-4T-1 to construct a prokaryotic expression vector pGEX-4T-1-VBMDMP.Recombinant VBMDMP produced in Escherichia coli has been shown to have significant activity of antitumor growth and antimetastasis in Lewis lung carcinoma transplanted into mouse C57B1/6.In the present study,we have studied the ability of rVBMDMP to inhibit endothelial cell tube formation and proliferation,to induce apoptosis in vitro,and to suppress tumor growth in vivo.The experimental results showed that rVBMDMP potently inhibited prolif- eration of human endothelial(HUVEC-12)cells and human colon cancer(SW480)cells in vitro,with no inhibition of proliferation in Chinese hamster ovary(CHO-K1)cells.rVBMDMP also significantly inhibited human endothelial cell tube formation and suppressed tumor growth of SW480 cells in a mouse xenograft model.These results suggest that rVBMDMP is a powerful therapeutic agent for suppressing angiogenesis and tumor growth.