Anticancer Therapeutic Potential of VEGI, an Antiangiogenic Cytokine

摘要

Vascular endothelial growth inhibitor (VEGI) is an endothelial cell- specific gene and a potent inhibitor of angiogenesis and tumor growth. We are now able to produce large quantities of one of the isoforms of VEGI, VEGI-192, in E. coli. The anticancer activity of VEGI-192 was evaluated with a Lewis lung cancer murine tumor model. Systemic administration of the recombinant protein to tumor-bearing C57BL black mice by intraperitoneal injection at 20 mg/Kg, two times a week, gave rise to a marked inhibition of tumor growth. Similar efficacy was observed in the treatment of both early and late stages of the established tumors. As much as 50% inhibition of the tumor growth rate was achieved when the tumor volumes reached nearly 5% of the body weight at the time of the initiation of the treatment. Inhibition of tumor formation was also observed when the recombinant protein was given at the time of cancer cell inoculation. Immunohistochemical analysis of the tumor vasculature indicated that VEGI treatment specifically eliminated endothelial cells. Vascular smooth muscle cells in contrast were largely unaffected, and remained associated with a residual vascular structure consisting of blood vessel basement membrane. These results demonstrate the potential of recombinant VEGI-192 as a therapeutic agent for cancer treatment.