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 C57Bl/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 proliferation 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.
Cao
Jian-Guo
JG
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, China. Caojianguo2005@yahoo.com.cn
Peng
Shu-Ping
SP
Sun
Li
L
Li
Hui
H
Wang
Li
L
Deng
Han-Wu
HW
D020533:Angiogenesis Inhibitors / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001324:Autoantigens / Q000235:genetics / Q000494:pharmacology*; D001485:Basement Membrane / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D024141:Collagen Type IV / Q000235:genetics / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000473:pathology*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009389:Neovascularization, Pathologic; D010455:Peptides / Q000494:pharmacology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D001324:Autoantigens; D024141:Collagen Type IV; D007074:Immunoglobulin G; D010455:Peptides; D011993:Recombinant Fusion Proteins; C057112:type IV collagen alpha3 chain