Exosomes serve as nanoparticles to suppress tumor growth and angiogenesis in gastric cancer by delivering hepatocyte growth factor siRNA

Cancer Sci. 2018 Mar;109(3):629-641. doi: 10.1111/cas.13488. Epub 2018 Feb 11.

Abstract

Exosomes derived from cells have been found to mediate signal transduction between cells and to act as efficient carriers to deliver drugs and small RNA. Hepatocyte growth factor (HGF) is known to promote the growth of both cancer cells and vascular cells, and the HGF-cMET pathway is a potential clinical target. Here, we characterized the inhibitory effect of HGF siRNA on tumor growth and angiogenesis in gastric cancer. In addition, we showed that HGF siRNA packed in exosomes can be transported into cancer cells, where it dramatically downregulates HGF expression. A cell co-culture model was used to show that exosomes loaded with HGF siRNA suppress proliferation and migration of both cancer cells and vascular cells. Moreover, exosomes were able to transfer HGF siRNA in vivo, decreasing the growth rates of tumors and blood vessels. The results of our study demonstrate that exosomes have potential for use in targeted cancer therapy by delivering siRNA.

Keywords: angiogenesis; exosomes; hepatocyte growth factor; siRNA; tumor therapy.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Coculture Techniques
  • Exosomes / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Hepatocyte Growth Factor / antagonists & inhibitors
  • Hepatocyte Growth Factor / genetics*
  • Humans
  • Mice
  • Nanoparticles
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / pharmacology
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Up-Regulation / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • HGF protein, human
  • RNA, Small Interfering
  • Hepatocyte Growth Factor