Inhibitory Effect On Colon Cancer By Combination Of Endostatin, SU6668 And 5-Fu In Nude Mice

Objective To study the effect of angiogenesis inhibitors Endostatin, SU6668 plus 5-Fu on the growth and metastasis of human colon cancer xenografts in nude mice.Methods Metastatic model of human colon cancer was established by orthotopic implantation of human tumor tissue into colonic wall of nude mice.Twelve days later, sixty mice were randomly divided into five groups, saline water (control group), Endostatin (E), SU6668 (S), Endostatin plus SU6668 (E+S) , Endostatin plus SU6668 plus 5-Fu (E+S+F) were administered by intraperitoneal injected every day for 28 days.42 days after implantation, the tumor weight,inhibition rates, and metastasis were evaluated after the mice sacrificed by cervical dislocation. Immunohistochemical staining was employed to determine intratumoral microvessel density (MVD).Results Compared with the control, tumor growth was significantly inhibited in mice of group E, S, E+S and E+S+F with inhibition rate (%) of 0, 48.5, 44.9, 59.6, and 66.9 respectively. MVD decreased significantly in treated groups (13.0±1.33, 4.00±0.40, 4.10±0.40, 2.19±0.26 and 1.38±0.19). The incidences (%) of peritoneal and region lymph node metastases were also significantly inhibited in group E, S, E+S and E+S+F (70, 8.3, 18.2, 0, and 0; 90, 0, 0, 0 and 0). The growth and metastasis of human colon cancer implanted in nude mice were inhibited in group E, S, E+S and E+S+F, especially in group E+S+F.Conclusion The angiogenesis inhibitors Endostatin and SU6668 in combination with 5-Fu has an synergistic effect and strong inhibitory activity against humor growth and metastasis of human colon cancer xenografts in mice.