Anti-metastasis efficacy and safety of non-anticoagulant heparin derivative versus low molecular weight heparin in surgical pancreatic cancer models

  • Authors:
    • Reem Alyahya
    • Thangirala Sudha
    • Michael Racz
    • Steven C. Stain
    • Shaker A. Mousa
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  • Published online on: December 19, 2014     https://doi.org/10.3892/ijo.2014.2803
  • Pages: 1225-1231
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Abstract

Heparin and its derivatives are known to attenuate cancer metastasis in preclinical models, but have not been used clinically due to adverse bleeding effects. This study compared the efficacy of S-NACH (a sulfated non-anticoagulant heparin) versus tinzaparin (a low molecular weight heparin) in inhibiting metastasis of a growing primary tumor and following surgical excision of primary tumor in a pancreatic cancer mouse model. The efficacy of S-NACH versus tinzaparin on metastasis of the primary tumor was evaluated in each experiment using IVIS imaging. Athymic female mice were treated with S-NACH or tinzaparin, and 30 min later luciferase-transfected pancreatic cancer cells (Mpanc96) were implanted into the spleen; treatment was continued daily until termination. Next we studied the effect of S-NACH versus tinzaparin on metastasis after surgical excision of the primary tumor after 3 weeks of daily treatment with S-NACH or tinzaparin. S-NACH reduced surgically induced metastasis (p<0.01) and tumor recurrence (p<0.05) relative to control. Histopathological studies demonstrated significant increase in tumor necrosis mediated by S-NACH and to lesser extent by tinzaparin as compared to control group. Furthermore, either S-NACH or tinzaparin upregulated the expression of the junctional adhesion molecule E-cadherin in pancreatic cancer cells where its low expression enhances cancer cell migration and invasion. In terms of bleeding time (BT), S-NACH did not affect BT as compared to tinzaparin, which doubled BT. These data suggest that S-NACH is an effective and safe anti-metastatic agent and warrants further clinical evaluation.
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March-2015
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Spandidos Publications style
Alyahya R, Sudha T, Racz M, Stain SC and Mousa SA: Anti-metastasis efficacy and safety of non-anticoagulant heparin derivative versus low molecular weight heparin in surgical pancreatic cancer models. Int J Oncol 46: 1225-1231, 2015
APA
Alyahya, R., Sudha, T., Racz, M., Stain, S.C., & Mousa, S.A. (2015). Anti-metastasis efficacy and safety of non-anticoagulant heparin derivative versus low molecular weight heparin in surgical pancreatic cancer models. International Journal of Oncology, 46, 1225-1231. https://doi.org/10.3892/ijo.2014.2803
MLA
Alyahya, R., Sudha, T., Racz, M., Stain, S. C., Mousa, S. A."Anti-metastasis efficacy and safety of non-anticoagulant heparin derivative versus low molecular weight heparin in surgical pancreatic cancer models". International Journal of Oncology 46.3 (2015): 1225-1231.
Chicago
Alyahya, R., Sudha, T., Racz, M., Stain, S. C., Mousa, S. A."Anti-metastasis efficacy and safety of non-anticoagulant heparin derivative versus low molecular weight heparin in surgical pancreatic cancer models". International Journal of Oncology 46, no. 3 (2015): 1225-1231. https://doi.org/10.3892/ijo.2014.2803