Exosomes-coated bcl-2 siRNA inhibits the growth of digestive system tumors both in vitro and in vivo

Int J Biol Macromol. 2020 Oct 15:161:470-480. doi: 10.1016/j.ijbiomac.2020.06.052. Epub 2020 Jun 9.

Abstract

Background: The therapeutic application of small interfering RNA is limited by the lack of an effective delivery system to tumors. In the present study, an efficient approach to deliver siRNA to cancer cells using exosome system was developed.

Materials & methods: Exosomes were isolated from bovine milk and exosomes-coated bcl-2 siRNA (exosiBcl-2) was synthesized using ultrasonic approach. The anticancer effect of exsosiBcl-2 was studied by Confocal microscopy, flow cytometry, scratch wound healing and Transwell experiments, RT-qPCR and Western blot approaches, etc. Xenograft nude mice tumor model was performed to check the antitumor activity of exosiBcl-2 in vivo.

Results: ExosiBcl-2 can cross the cell membrane efficiently and inhibit the growth of cancer cells. ExosiBcl-2 treatment led to apoptosis and dramatic inhibition of migration and invasion of cancer cells via downregulating metastatic related genes. In vivo study revealed that exosiBcl-2 inhibited the tumor growth significantly in nude mice.

Conclusion: ExosiBcl-2 has potential to be developed as a novel anticancer agent.

Keywords: Bcl-2 siRNA; Digestive system tumor; Exosomes.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cattle
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Digestive System Neoplasms / drug therapy*
  • Down-Regulation / drug effects
  • Exosomes / chemistry*
  • Female
  • HCT116 Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Proto-Oncogene Proteins c-bcl-2 / genetics*
  • RNA, Small Interfering / genetics*
  • RNA, Small Interfering / pharmacology*
  • Xenograft Model Antitumor Assays / methods

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering