Effect of Fraxiparine and heparin on experimental tumor metastasis in mice
Béla Szende1, Sándor Paku, Gergely Rácz
1First Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary. bszende@korb1.sote.hu
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.
Insights
Fraxiparine, a low molecular weight heparin (LMWH), demonstrated significant antimetastatic effects in mouse models. This finding suggests potential applications for LMWH in anticoagulant cancer therapy.
Area of Science:
- Pharmacology
- Oncology
- Hematology
Background:
- Low molecular weight heparins (LMWH) are crucial in anticoagulant therapy.
- Heparin and LMWH derivatives have shown potential antitumor and antimetastatic activities.
Purpose of the Study:
- To evaluate the antimetastatic efficacy of Fraxiparine, a modified LMWH.
- To assess Fraxiparine's effects in various murine cancer metastasis models.
Main Methods:
- Fraxiparine was tested in intravenous, intra-foot pad, and intrasplenic metastasis models in C57 Bl/6 mice.
- Different doses of Fraxiparine and heparin (positive control) were administered pre- and post-tumor inoculation.
- Treatment strategies included single-dose and continuous administration protocols.
Main Results:
- Fraxiparine (57 IU/kg) significantly reduced metastasis in the intravenous model.
- Continuous Fraxiparine treatment (173 IU/kg) strongly inhibited lung metastases in the intra-foot pad model.
- Fraxiparine was ineffective in the intrasplenic model, and heparin showed no significant effect on metastasis.
Conclusions:
- Fraxiparine exhibits significant antimetastatic properties in specific murine models.
- These findings hold potential implications for anticoagulant treatment strategies in cancer patients.
