Antiangiogenic therapy for human pancreatic carcinoma xenografts in nude mice
摘要
AIM: To investigate the anti-tumor effects of antiangiogenic therapy (a combination of TNP-470, an antiangiogenic compound, with gemcitabine, an antimetabolite) on human pancreatic carcinoma xenografts and its mechanism.METHODS: A surgical orthotopic implantation (SOI) model was established by suturing small pieces of SW1990pancreatic carcinoma into the tail of pancreas in nude male mice. Mice then received either single therapy (n = 24) or combined therapy (n = 32). Mice receiving single therapy were randomly divided into control group, G100 group receiving 100 mg/kg gemcitabine IP on d 0, 3, 6 and 9after transplantation, and T30 group receiving 30 mg/kg TNP-470 s.c on alternate days for 8 wk. Mice receiving combined therapy were randomly divided into control group,T15 group, GS0 group and combination group (TNP-47030 mg/kg and gemcitabine 50 mg/kg). Animals were killed 8 wk after transplantation. Transplanted tumors, liver,lymph node and peritoneum were removed. Weight of transplanted tumors, the T/C rate (the rate of mean treated tumor weight to mean control tumor weight), change of body weight, metastasis rate, and 9-wk survival rate were investigated. Tumor samples were taken from the control group, T30 group, G100 group and combination group.PCNA index (PI) and microvessel density (MVD) were investigated by immunohistochemical staining for PCNA and factor Ⅷ, respectively.RESULTS: There was a significant inhibitory effect on primary tumor growth of pancreatic carcinoma in G100group, compared to T30 group, whereas tumor metastasis was significantly inhibited in T30 group compared to G100group. There was no significant improvement in survival rate in these two groups. No significant inhibitory effect on tumor growth and metastasis in T15 group and G50 group.However, significant anti-tumor and anti-metastatic effects were observed in the combination group with a significant improvement in survival rate. The inhibitory effect on tumor growth in combination group en