Polyinosinic-polycytidylic acid liposome induces human hepatoma cells apoptosis which correlates to the up-regulation of RIG-I like receptors

Cancer Sci. 2009 Mar;100(3):529-36. doi: 10.1111/j.1349-7006.2008.01062.x. Epub 2008 Dec 22.

Abstract

Toll-like receptor 3 and RIG-I like receptors (RLRs; MDA5, RIG-I) are involved in cell growth inhibition and apoptosis. However, the toll-like receptor 3-related apoptotic pathway is insensitive to direct polyinosinic-polycytidylic acid (dsRNA analog) stimulation in hepatoma cells. To determine whether the strategy of transferring polyinosinic-polycytidylic acid into cells (polyinosinic-polycytidylic acid-liposome) could induce apoptosis in hepatoma cells through cytoplasm receptors, we examined the responses of innate immune receptors RLRs and toll-like receptor 3 in response to different stimulation. We found that the apoptosis could exclusively be detected under polyinosinic-polycytidylic acid-liposome stimulation, which involved the activation of the caspase pathway. Besides, the expression of RIG-I, MDA5, IFNbeta and interferon-stimulated gene 15 was increased significantly at an early stage. Moreover, the growth inhibition of polyinosinic-polycytidylic acid-liposome was confirmed in a mouse model. Taken together, these results suggest polyinosinic-polycytidylic acid-liposome could be used as a potential apoptotic agent in hepatocellular carcinoma cells and imply a potential therapeutic strategy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Carcinoma, Hepatocellular / metabolism*
  • Caspases / drug effects
  • Cell Line, Tumor
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / drug effects*
  • Flow Cytometry
  • Humans
  • Interferon Inducers / administration & dosage*
  • Interferon-Induced Helicase, IFIH1
  • Interferon-beta / drug effects
  • Liposomes
  • Liver Neoplasms / metabolism*
  • Male
  • Mice
  • Mice, Nude
  • Poly I-C / administration & dosage*
  • RNA, Messenger / analysis
  • Receptors, Immunologic
  • Reverse Transcriptase Polymerase Chain Reaction
  • Up-Regulation
  • Xenograft Model Antitumor Assays

Substances

  • Interferon Inducers
  • Liposomes
  • RNA, Messenger
  • Receptors, Immunologic
  • Interferon-beta
  • Caspases
  • RIGI protein, human
  • IFIH1 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Interferon-Induced Helicase, IFIH1
  • Poly I-C