[Inhibition of growth and metastases of human colon cancer xenograft in nude mice by angiogenesis inhibitor endostatin].
OBJECTIVE
Tumor angiogenesis is essential for growth and metastases of colon cancer. Angiogenesis inhibitors can induce apoptosis in colon cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastases of human colon cancer. Anti-angiogenic cancer therapy is important for selecting the timing and method of operation and program of complex treatment and enhancing the five-year survival rate of patients with colon cancer. In this study, we aimed to investigate the effects of angiogenesis inhibitor endostatin on the growth and metastases 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. Endostatin was administered s.c. at dose 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 (AI) and the presence of metastases are evaluated respectively after the mice were sacrificed.


RESULTS
In compared with the untreated controls, growth of the orthotopically implanted tumor was 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 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 AI 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 metastases to the liver and peritoneaum were also significantly inhibited in a dose-dependent manner (P < 0.05).


CONCLUSIONS
Angiogenesis inhibitor endostatin can induce apoptosis in colon cancer by inhibiting tumor angiogenesis and has strong inhibitory effect both on tumor growth and metastases of human colon cancer xenograft in nude mice.
Zhang
Guo-feng
GF
Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P. R. China. zhangguofengmd@sina.com
Wang
Yuan-he
YH
Zhang
Ming-ao
MA
Wang
Qiang
Q
Luo
Yun-bao
YB
Wang
Deng-shan
DS
Han
Ce-ran
CR
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D003094:Collagen / Q000008:administration & dosage / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology; D043169:Endostatins; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010446:Peptide Fragments / Q000008:administration & dosage / Q000627:therapeutic use*; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D043169:Endostatins; D010446:Peptide Fragments; D003094:Collagen