Effect of Fraxiparine and Heparin on Experimental Tumor Metastasis in Mice

Abstract

Background: Low molecular weight heparins (LMWH) have become increasingly important in anticoagulant therapy. Antitumor and antimetastatic activity of heparin and LMWH-s have also been reported. Materials and Methods: Fraxiparine, a new modified LMW-H, was tested for antimetastatic effect using 3LL-HH intravenous, B₁₆ intra-foot pad and 3LL-HH intrasplenic models in C₅₇ Bl/6 mice. The dose of Fraxiparine was 38, 57 and 172 IU/kg, respectively. Heparin (100 IU/kg) was used as a positive control. Both pre-treatment (starting 6 hours before tumor inoculation) and post-treatment (starting 24 hours after tumor inoculation), followed by daily injections, were applied in the intra-foot pad and intrasplenic models. In the intravenous model, only a single dose was administered one hour after tumor cell injection. Results: Fraxiparine at the dose of 57 IU/kg was significantly antimetastatic in the intravenous model. Continuous treatment, starting 6 hours before tumor inoculation, with 173 IU/kg Fraxiparine resulted in a strong inhibition of lung metastases in the intra-foot pad model, but was ineffective in the intrasplenic model. Heparin did not influence the metastasis number in any of the metastasis models. Conclusion: These data may be of importance in the anticoagulant treatment of human cancer patients.