Suppression of pancreatic cancer by sulfated non-anticoagulant low molecular weight heparin

Cancer Lett. 2014 Aug 1;350(1-2):25-33. doi: 10.1016/j.canlet.2014.04.016. Epub 2014 Apr 24.

Abstract

Sulfated non-anticoagulant heparins (S-NACHs) might be preferred for potential clinical use in cancer patients without affecting hemostasis as compared to low molecular weight heparins (LMWHs). We investigated anti-tumor effects, anti-angiogenesis effects, and mechanisms of S-NACH in a mouse model of pancreatic cancer as compared to the LMWH tinzaparin. S-NACH or tinzaparin with or without gemcitabine were administered, and tumor luminescent signal intensity, tumor weight, and histopathology were assessed at the termination of the study. S-NACH and LMWH efficiently inhibited tumor growth and metastasis, without any observed bleeding events with S-NACH as compared to tinzaparin. S-NACH distinctly increased tumor necrosis and enhanced gemcitabine response in the mouse pancreatic cancer models. These data suggest the potential implication of S-NACH as a neoadjuvant in pancreatic cancer.

Keywords: Anti-cancer; Low molecular weight heparin; Non-anticoagulant heparin; Pancreatic cancer; Tumor suppressor; Tumor survival.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Cell Line, Tumor
  • Chick Embryo
  • Chorioallantoic Membrane / drug effects
  • Deoxycytidine / analogs & derivatives
  • Deoxycytidine / therapeutic use
  • Enzyme Inhibitors / therapeutic use
  • Female
  • Fibrinolytic Agents / therapeutic use*
  • Gemcitabine
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Metastasis
  • Neovascularization, Pathologic / drug therapy
  • Pancreatic Neoplasms / drug therapy*
  • Tinzaparin
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Enzyme Inhibitors
  • Fibrinolytic Agents
  • Heparin, Low-Molecular-Weight
  • Deoxycytidine
  • Tinzaparin
  • Gemcitabine