Experimental Studies On Antiangiogenic Colon Cancer Therapy

Tumor angiogenesis is essential for growth and metastasis of colon cancer. Angiogenesis inhibitors can induce apoptosis in colon cancer by inhibiting tumor angiogenesis and have strong inhibitory effect both on tumor growth and metastasis of human colon cancer. Anti-angiogenic cancer therapy is important for selecting the timing and method of operation and the program of complex treatment and enhancing the five-year survival rate of patients with colon cacer. This experimental study on antiangiogenic colon cancer therapy included four parts.1 . Establishment of orthotopic implant and metastatic model of human colon cancer xenograft in nude miceObjective To establish an orthotopic implant and metastatic model of human colon cancer xenograft in nude mice.Methods Tumor cell line SW1116 of human colon adenocarcinoma was inoculated subcutaneously into nude mice to develop implant-tumor. Histologically intact tumor tissue was then collected. Metastatic model simulating human colon cancer was established by orthotopic implantation of histologically intact human tumor tissue into colon wall of nude mice. The local tumor growth characteristics, tumor-take rates and metastasis rates were examined.Results A 100% tumor-take rate was obtained in the model. The incidences of local nodes, peritoneal and liver metastases were 100%, 91.7% and 75.0% respectively. The median survival period of the tumor-bearing nude mice was 10 weeks. Emaciation and exhaustion of the nude mice were presented in late stage of the experiment.Conclusion The orthotopic implant and metastatic model provide a useful tool for study on the mechanism of metastasis and treatment of human colon cancer.2 . Inhibition of growth and metastasis of human colon cancer implanted in nude mice by endostatinObjective To investigate the effects of angiogenesis inhibitor Endostatin on thegrowth and metastasis of human colon cancer in vivo.Methods Metastatic model simulating human colon cancer was established by orthotopic implantation of histologically intact human tumor tissue into the colon wall of nude mice. Endostatin was administered sc at dosage of 0 mg/kg, 5 mg/kg, 10 mg/kg and 20 mg/kg every day for six weeks. Seven weeks after implantation, the tumor weight and inhibition rates and intratumoral microvessel density (MVD) and apoptotic index (A I) and the presence of metastasis are evaluated respectively after the mice were sacrificed.Results Compared with the untreated controls, growth of the orthotopically implanted tumors were significantly reduced in weight in mice treated with endostatin with an inhibition rate of 0%, 67.9%, 84.0% and 90.1% at the dosage of 0 mg/kg, 5 mg/kg, 10 mg/kg, and 20 mg/kg , respectively. The MVD was also decreased significantly in the treated mice [(12.8 4.1) versus (5.9 2.5), (2.2 1.4) and (0.74 0.3)]. The Al was increased significantly in the treated mice [(3.87 2.61)%, versus (6.89 5.18)%, (13.24 4.76)% and (20.97 9.04)%]. The incidences of peritoneal metastases were also significantly inhibited in the treated mice (90.0% versus 36.4%, 25.0% and 0%). The incidences of liver metastases were also significantly inhibited in the treated mice (80.0% versus 27.3%, 16.7% and 0%). Tumor metastasis to the liver and peritoneaum was also significantly inhibited in a dose-dependent manner (P < 0.05).Conclusion Angiogenesis inhibitor Endostatin can induce apoptosis in colon cancer by inhibiting tumor angiogenesis and has strong inhibitory effect on both tumor growth and metastasis of human colon cancer implanted in nude mice.3 . Inhibition of growth and metastasis of human colon cancer implanted in nude mice by SU6668Objective To study the effects of angiogenesis inhibitor SU6668 on the growth and metastasis of colon cancer in vivo.Methods Metastatic model simulating human colon cancer was established by orthotopic implantation of histologically intact human tumor tissue into colon wall of nude mice. Mice were randomly divided into 4 groups (n=12): control group (salinesolution...