抗血管生成药物Endostatin和SU6668联合氟尿嘧啶对结肠癌的影响

Effect of Endostatin and SU6668 combined with 5-FU on human colon cancer xenograft in nude mice

目的探讨血管生成抑制剂Endostatin和SU6668联合氟尿嘧啶（5-FU）对结肠癌生长和转移的抑制作用，并探讨其作用机制。方法建立人结肠癌裸鼠原位种植转移模型。将60只荷瘤鼠随机分为5组，每组12只。种植12d后分别自腹腔内注射生理盐水（对照组）、Endostatin（E组）、SU6668（S组）、Endostatin加SU6668（E加S组）、Endostatin加SU6668加5-FU（E加S加F组），1次／d，共4周。种植后第6周末处死动物，测量原位肿瘤瘤重、抑瘤率和肿瘤微血管密度（MVD），观察肿瘤肝腹膜和区域淋巴结转移及腹水出现情况。结果对照组、E组、S组、E加S组、E加S加F组抑瘤率分别为0、64．9％、63．5％、76．4％和88．2％；MVD分别为（18．10±5．65）、（2．75±0．75）、（3．17±0．58）、（0．94±0．42）和（0．36±0．45）；腹膜转移率分别为90％、16．7％、25％、0和0；区域淋巴结转移率分别为90％、0、0、0和0。E组、S组、E加S组、E加S加F组与对照组相比，结肠癌生长和转移受到明显抑制（P〈0．05）；尤以E加S加F组明显（P〈0．01）。结论Endostatin和SU6668联合5-FU具有协同作用，能更有效地抑制结肠癌的生长和转移。

Objective To investigate the effect of Endostatin and SU6668 combined with 5-FU on the growth and metastasis of human colon cancer in vivo and its mechanism. Methods Metastatic model of human colon cancer was established by orthotopic implantation of human tumor tissue into colon wall of nude mice. Twelve days later, mice were randomly divided into saline water control, Ensostatin, SU6668, Ensostatin plus SU6668, and Endostatin plus SU6668 and 5-FU groups, intraperitoneal injected respectively every day for four weeks. Six weeks after implication, the tumor weight, inhibition rates, intratumoral microvessel density （MVD） and metastasis were evaluated after the mice were sacrificed. Results Compared with the control, tumor growth was significantly inhibited in mice treated respectively with Ensostatin, SU6668, Ensostatin plus SU6668 and Endostatin plus SU6668 and 5-FU with an inhibition rate of 0, 64.9%, 63.5%, 76.4% and 88.2% respectively, and MVD decreased significantly in treated groups [ （18.10±5.65） vs （2.75±0.75）, （3.17±0.58）, （0.94±0.42） and （0.36±0.45）]. The incidences of peritoneal and region lymph node metastases were significantly inhibited in Ensostatin, SU6668, Ensostatin plus SU6668 and Endostatin plus SU6668 and 5-FU （90% vs 16.7%, 25%, 0 and 0; 90% vs 0, 0, 0 and 0）. The growth and metastasis of human colon cancer implanted in nude mice were significantly inhibited in Ensostatin, SU6668, Ensostatin plus SU6668, and Endostatin plus SU6668 and 5-FU, and the effect of Endostatin plus SU6668 and 5-FU was the most obviously. Conclusion Endostatin plus SU6668 and 5-FU has strong inhibitory effect both on tumor growth and metastasis of human colon cancer.