Article
Effective tumor therapy with coagulation active Antithrombin III in a human pancreatic cancer xenograft model in SCID mice
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Published: | March 20, 2006 |
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Background: Tumor growth is dependent upon the balance of positive and negative regulators of angiogenesis. Antiangiogenic compounds such as antiangiogenic Antithrombin III (aaAT III) inhibit endothelial cell biology in vitro and angiogenesis in vivo. Until now it is unknown whether coagulation active Antithrombin (AT III) is effective as an antiangiogenic inhibitor. The aim of the study was to determine the effect of coagulation active AT III (KyberninÓ) on the growth of human pancreatic cancer in a mouse model (SCID).
Material and methods: A human pancreatic cancer cell line (BxPC3) was injected subcutaneously into the dorsa of male, immunodeficient (SCID) mice. When tumor volume was 100 mm3, mice were randomized into five groups (n=8/group) receiving systemic (s.c.) KyberninÓ (10; 50; 100 mg/kg /day with n=8 /group), latent AT III (antiangiogenic AT III) (100 mg/kg/day with n=4/group) injections or Buffer (n=5/group) as control for 20 days. Tumors were measured every third day and the ratio of treated to control tumor volume (T/C) was determined for the last time point. Descriptive and explorative statistical analysis was performed.
Results: After 20 days of treatment the tumor volume in the group that received Buffer was 1741+/-557 mm3 versus 335+/- 63 mm3 for those being treated with KyberninÓ 100 mg/kg/day; 166+/- 25 mm3 when treated with KyberninÓ 50 mg/kg/day ; 538 +/- 40 mm3 when treated with KyberninÓ 10 mg/kg/day and 349 +/- 65 mm3 for treatment with latent AT III (100 mg/kg/day). The T/C ratio (treatment/control) decreased progressively during the experiments, and was 0.19 for KyberninÓ 100 mg/kg/day, 0.10 for 50 mg/kg/day, 0.31 for 10 mg/kg/day and 0.20 for latent AT III (100 mg/kg/day). The inhibition of tumor growth was statistically significant in all treatment groups compared to placebo. All mice gained weight throughout the study.
Conclusion: Coagulation active AT III (KyberninÓ) was effective in this mouse tumor model of pancreatic cancer. The most effective dosage was 50 mg/kg/day. Based on this results and further preclinical investigations, clinical trials with coagulation active AT III (KyberninÓ) in cancer patients might be of interest.