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

硫酸化非抗凝低分子量肝素对胰腺癌的抑制

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作者:Thangirala Sudha, Murat Yalcin, Hung-Yun Lin, Ahmed M Elmetwally, Tipu Nazeer, Thiruvengadam Arumugam, Patricia Phillips, Shaker A Mousa

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.

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