VBMDMP论文..doc

Vascular Basement Membrane Derived Multifunctional Peptide, a Novel Inhibitor of Angiogenesis and Tumor Growth* Jian-Guo CAO1,2, Shu-Ping PENG1, Li SUN2, Hui LI2, Li WANG2, Han –Wu DENG#1 (1 Department of Pharmacology，School of Pharmaceutical Sciences ， Central South University, Changsha, Hunan 410078，China 2 Cancer Research Institute of Nanhua University, Heng Yang, Hunan 421001，China) Abstract Vascular basement membrane-derived multifunctional peptide (VBMDMP) sequence (fusion gene of human IgG3 upper hinge region and two tumstatin-derived fragments) obtained by artificial synthesis was cloned into Vector pUC19, was introduced into an expression Vector pGEX-4T-1 to construct a prokaryotic expression Vector pGEX-4T-1-VBMDMP. VBMDMP was produced as a recombinant molecule in Escherichia coli. rVBMDMP has been proved to have significant biological activity of anti-tumor growth and anti-metastasis in Lewis lung carcinoma transplanted into mouse C57BL/6. In the present study, we demonstrate the ability of rVBMDMP, to inhibit endothelial cell tube formation, proliferation and to induce apoptosis in vitro, as well as suppress tumor growth in vivo. rVBMDMP potently inhibited proliferation of human endothelial (HUVEC-12) cells and human colon cancer (SW480) cells in vitro, with no inhibition of proliferation observed on Chinese hamster Ovary (CHO-K1) cells. Additionally, rVBMDMP significantly inhibited human endothelial cell tube formation and suppressed tumor growth of human colon cancer cell (SW480) in mouse xenograft model. Collectively these results suggest that rVBMDMP is a powerful therapeutic molecule for suppressing angiogenesis and tumor growth. Key Words: recombinant Vascular basement membrane derived multifunctional peptide; angiogenesis inhibitor; therapeutical action *This work is supported by National Natural Science Foundation of China (General Program No.. *This work is supported by Key Program of the Health Department of Hunan Province