VEGF165b the anti‐angiogenic isoform of VEGF inhibits tumor growth in vivo.

Abstract

To determine the potential of the anti‐angiogenic isoform,VEGF165b for cancer therapy, we compared the inhibitory effects of recombinant human VEGF165b on mouse model of colon cancer with bevacizumab. 2x106 LS174T human colon carcinoma cells were injected subcutaneously (SC) into the intrascapular dorsal region of nude mice. Tumor‐bearing mice were injected intraperitoneally (IP) with saline or bevacizumab (50 ?g), or SC in the lumbar region with 100 ?g VEGF165b bi‐weekly for 2 weeks. The inhibitory concentration of the IC50 was calculated. Growth of tumors was significantly suppressed by SC VEGF165b injection compared to those treated by saline (p<0.001) or bevacizumab (p<0.001), which also significantly reduced tumor growth (p<0001, 2 way ANOVA). SC injection of VEGF165b resulted in a significant reduction of tumor volume from 254±51mm3 to 35.4±17mm3 after injection (p<0.01 compared with before treatment, rmANOVA, Dunnets), whereas bevacizumab stabilised tumor growth (231±22 before compared with 342.± 117mm3, NS). Tumors in saline treated mice grew significantly from 149±46 to 853±362mm3, (p<0.001). The IC50 of VEGF165b was calculated to be 48µg. Administration of VEGF165b inhibits the growth of colon cancer in vivo and indicates that systemic therapy of VEGF165b may be an effective anti‐VEGF tool for the treatment of colon cancer. This work supported by AICR and PhiloGene Inc.