Carboxymethyl chitosan represses tumor angiogenesis in vitro and in vivo

Carbohydr Polym. 2015 Sep 20:129:1-8. doi: 10.1016/j.carbpol.2015.04.040. Epub 2015 Apr 27.

Abstract

Carboxymethyl chitosan (CMCS), with potent water solubility, biocompatibility, and non-toxicity, has emerged as a promising candidate for biomedical applications. In this study, the anti-tumor angiogenesis effects of CMCS were evaluated in vitro and in vivo. Our results showed that CMCS could inhibit the 2-dimensional and 3-dimensional migration of human umbilical vein endothelial cells (HUVECs) in vitro. CMCS significantly inhibited the growth of mouse hepatocarcinoma 22 tissues and could promote tumor cell necrosis as suggested by pathological observations. The CD34 expression in H22 tumor tissue, the levels of vascular endothelial growth factor and tissue inhibitor of metalloproteinase 1 in serum was regulated by CMCS treatment. CMCS could significantly improve thymus index, spleen index, tumor necrosis factor α and interferon γ level. In a conclusion, CMCS possessed potent anti-tumor effects by inhibiting tumor angiogenesis, stimulating immune functions. Our date provide more foundation for application of CMCS in biomedicine or biomaterials for targeted anticancer drugs delivery.

Keywords: Angiogenesis; Anti-tumor; Carboxymethyl chitosan; In vitro; In vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD34 / metabolism
  • Carcinoma, Hepatocellular / blood
  • Carcinoma, Hepatocellular / blood supply*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Chitosan / analogs & derivatives*
  • Chitosan / pharmacology
  • Chitosan / therapeutic use
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Immunohistochemistry
  • Interferon-gamma / blood
  • Liver Neoplasms / blood
  • Liver Neoplasms / blood supply*
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Mice
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / pathology
  • Spectrophotometry, Infrared
  • Spleen / drug effects
  • Spleen / metabolism
  • Thymus Gland / drug effects
  • Thymus Gland / metabolism
  • Tissue Inhibitor of Metalloproteinase-1 / blood
  • Tumor Necrosis Factor-alpha / blood
  • Vascular Endothelial Growth Factor A / blood

Substances

  • Antigens, CD34
  • Tissue Inhibitor of Metalloproteinase-1
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • carboxymethyl-chitosan
  • Interferon-gamma
  • Chitosan