Combination of attenuated Salmonella carrying PD-1 siRNA with nifuroxazide for colon cancer therapy

J Cell Biochem. 2020 Feb;121(2):1973-1985. doi: 10.1002/jcb.29432. Epub 2019 Nov 6.

Abstract

Colon cancer is a member of malignant tumors in the digestive system. Traditional treatment strategies are ineffective and improving the treatment of colon cancer is an urgent need. Targeting programmed cell death-1 (PD-1) by monoclonal antibodies has shown some therapeutic effectiveness and has advantages. Additionally, the Stat3 inhibitor nifuroxazide was employed to promote the antitumor activity. Here, we hypothesized that combining nifuroxazide with PD-1 small interfering RNA carried by attenuated Salmonella would exert a synergistic antitumor effect on colon cancer. Indeed, treatment with this combination effectively inhibited the development of colon cancer in mice and improved the survival rate. These two novel anticancer agents worked synergistically to elicit potent antitumor immunity and achieve improved therapeutic efficacy. The underlying mechanisms are mainly involved with immune regulation and cell apoptosis. This study provides a previous framework for combining this Stat3 inhibitor with RNAi designed to block immune checkpoint signaling for cancer therapy.

Keywords: PD-1; Salmonella; colon cancer; combination therapy; nifuroxazide; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Infective Agents / pharmacology
  • Apoptosis
  • Cell Movement
  • Cell Proliferation
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / therapy*
  • Combined Modality Therapy
  • Female
  • Humans
  • Hydroxybenzoates / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Nitrofurans / pharmacology*
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / genetics
  • RNA, Small Interfering / administration & dosage*
  • RNA, Small Interfering / genetics
  • Salmonella / chemistry*
  • Salmonella / genetics
  • Salmonella / growth & development
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Anti-Infective Agents
  • Hydroxybenzoates
  • Nitrofurans
  • Programmed Cell Death 1 Receptor
  • RNA, Small Interfering
  • nifuroxazide