Inhibitory effect of dsRNA TLR3 agonist in a rat hepatocellular carcinoma model

Mol Med Rep. 2013 Oct;8(4):1037-42. doi: 10.3892/mmr.2013.1646. Epub 2013 Aug 19.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common types of malignant tumor. Studies have demonstrated that the toll‑like receptor 3 (TLR3)/interferon pathway is inhibitory in cancer cell proliferation, suggesting that the activation of this pathway may have therapeutic potential. In the present study, the inhibitory effects of BM‑06, a double‑stranded (ds)RNA TLR3 agonist, against HCC were studied in vivo. Using a 2‑acetylaminofluorene-induced HCC rat model, histological examination and analysis of corresponding biomarkers following treatment with BM-06, showed a decrease in tumor growth and cell proliferation, and an increase in apoptosis compared with that in a phosphate‑buffered saline control group. In addition, the observed antitumor effect of BM‑06 in the HCC rat model was demonstrated to be superior to the known TLR3 agonist, polyinosinic-polycytidylic acid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Proliferation
  • Drug Screening Assays, Antitumor
  • Gene Expression
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism
  • Liver / pathology
  • Liver Neoplasms, Experimental / drug therapy*
  • Liver Neoplasms, Experimental / pathology
  • Male
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • RNA, Double-Stranded / pharmacology*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Toll-Like Receptor 3 / agonists
  • Tumor Burden / drug effects
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Antineoplastic Agents
  • BM-06
  • NF-kappa B
  • RNA, Double-Stranded
  • RNA, Messenger
  • TLR3 protein, rat
  • Toll-Like Receptor 3
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • Interferon-gamma
  • Casp8 protein, rat
  • Caspase 8