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

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, IFN beta 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. (Cancer Sci 2009; 100: 529-536).