Flk-1特异性蛋白激酶抑制剂SU5416阻断小鼠Lewis肿瘤新生血管形成并延长生存期

Flk-1 specific kinase inhibitor SU5416 blocked angiogenesis of Lewis carcinoma in mouse and prolonged the survival

Objective  To reveal the mechanism and effect of SU5416 in the treatment of mouse Lewis cancer in vivo. Methods  Lewis cell was transplanted into groin of C57/B6 mouse by subcutaneous injection, then SU5416 was administrated intraperitoneally to investigate the impact of SU5416 on tumor angiogenesis and growth in vivo. 32 mice were treated with SU5416 at two different doses every day until the end-point. As a control, 8 mice received no treatment and 8 mice were treated with vehicle (DMSO) only after implantation. Results  Median survival in the treated group was statistically longer compared to that in the control groups (P < 0.05) and no significant systemic adverse was observed. Histological analysis of the treated tumors showed an increase in necroses and reduced in angiogenesis compared to the control tumors. Furthermore, the percent of apoptotic cells increased in the treated tumors by FCM, the expressions of VEGF and KDR had no change after SU5416 administration by western blot. Conclusion  SU5416 may be useful therapeutics drug that specifically inhibits the enzymatic activity of KDR kinase and could down regulate the tumor angiogenesis. Supported by a grant from the National Key Project of Scientific and Technical Supporting Programs funded by Ministry of Science & Technology of China (No. 2006BAI02A05).