Inhibition of Liver Tumor Cell Metastasis by Partially Acetylated Chitosan Oligosaccharide on A Tumor-Vessel Microsystem

Mar Drugs. 2019 Jul 13;17(7):415. doi: 10.3390/md17070415.

Abstract

Chitooligosaccharides (COS), the only cationic oligosaccharide in nature, have been demonstrated to have anti-tumor activity. However, the inhibitory effects of COS on different stages of tumor metastasis are still unknown, and it is not clear what stage(s) of tumor metastasis COS targeted. To study the inhibitory effects of a new partially acetylated chitooligosaccharide (paCOS) with fraction of acetylation (FA) 0.46 on each phase of liver cancer cell metastasis, a dynamic tumor-vessel microsystem undergoing physiological flow was leveraged. paCOS (FA = 0.46) significantly inhibited proliferation of HepG2 cells through vascular absorption on the chip, and inhibited migration of HepG2 cells by inhibiting the formation of pseudopod in liver tumor cells. It was also found that paCOS at 10 μg/mL had a stronger inhibitory effect on liver tumor cells invading blood vessels than that of paCOS at 100 μg/mL, and paCOS at 100 μg/mL, which had a significant destructive effect on tumor vascular growth and barrier function. Moreover, paCOS reduced the number of liver tumor cells adhering onto the surface of HUVECs layer after 3 h of treatment. Therefore, the results revealed that paCOS had considerable potential as drugs for anti-tumor metastasis.

Keywords: dynamic tumor-vessel microsystem; liver tumor cell metastasis; partially acetylated chitooligosaccharides.

MeSH terms

  • Acetylation
  • Animals
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chitin / analogs & derivatives*
  • Chitin / chemistry
  • Chitin / pharmacology
  • Chitin / therapeutic use
  • Chitosan
  • Drug Screening Assays, Antitumor
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / blood supply
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / pathology
  • Microfluidic Analytical Techniques
  • Neoplasm Invasiveness / pathology
  • Neoplasm Invasiveness / prevention & control
  • Oligosaccharides
  • Tumor Microenvironment / drug effects*

Substances

  • Oligosaccharides
  • oligochitosan
  • Chitin
  • Chitosan