Recombinant vascular basement membrane derived multifunctional peptide blocks endothelial cell angiogenesis and neovascularization.
Angiogenesis is an innovative target in the therapy of cancer and other diseases, but the effects of anti-angiogenic drugs have been rather modest in clinical trials. We have developed a small peptide, recombinant vascular basement membrane derived multifunctional peptide (rVBMDMP), which significantly inhibits endothelial cells in vitro. Here we test the mechanisms of rVBMDMP in angiogenesis balance in assays of tubule formation, colony formation, and apoptosis in HUVE-12 endothelial cells. We also analyzed the differential expression of phosphorylation proteins and related genes in a protein phosphorylation chip and extracellular matrix adhesion molecule cDNA microarray, and validated changes with Western blot or real-time quantitative PCR, respectively. rVBMDMP dose-dependently inhibited colony formation, induced apoptosis, and inhibited in vitro tubule formation. rVBMDMP increased the phosphorylation of 88 signal proteins, including caspase-3, death receptor 3, 4, and 5, and integrin αV, β1, and β3, and down-regulated 41 signal proteins, including EGFR, pEGFR, VEGFR-1, and survivin versus control. rVBMDMP upregulated 14 genes, including collagen 4, 7, and 27, and down-regulated 21 genes, including integrin αVβ3, MMP10, and MMP12. Our study suggests that rVBMDMP inhibits angiogenesis and may be a viable drug candidate in anti-angiogenesis and anticancer therapies.
Wang
Chengkun
C
Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha 410078, Hunan, PR China.
Cao
Jianguo
J
Qu
Jiaquan
J
Li
Yafei
Y
Peng
Bo
B
Gu
Yixue
Y
He
Zhimin
Z
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000502:physiology*; D016326:Extracellular Matrix Proteins / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D010750:Phosphoproteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000494:pharmacology*; D015398:Signal Transduction / Q000235:genetics; D014471:Umbilical Veins / Q000166:cytology
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D016326:Extracellular Matrix Proteins; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; C540681:vascular basement membrane-derived multifunctional peptide