Peng Shuo, Geng Jianlin, Sun Rui, Tian Zhigang, Wei Haiming
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, School of Life Sciences, University of Science and Technology of China, Hefei, China.
Cancer Sci. 2009 Mar;100(3):529-36. doi: 10.1111/j.1349-7006.2008.01062.x. Epub 2008 Dec 22.
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.
Toll样受体3和维甲酸诱导基因I样受体（RLRs；黑色素瘤分化相关基因5、维甲酸诱导基因I）参与细胞生长抑制和凋亡。然而，Toll样受体3相关的凋亡途径对肝癌细胞中的直接聚肌苷酸-聚胞苷酸（双链RNA类似物）刺激不敏感。为了确定将聚肌苷酸-聚胞苷酸导入细胞的策略（聚肌苷酸-聚胞苷酸-脂质体）是否能通过细胞质受体诱导肝癌细胞凋亡，我们检测了天然免疫受体RLRs和Toll样受体3对不同刺激的反应。我们发现，仅在聚肌苷酸-聚胞苷酸-脂质体刺激下可检测到凋亡，这涉及半胱天冬酶途径的激活。此外，维甲酸诱导基因I、黑色素瘤分化相关基因5、β干扰素和干扰素刺激基因15的表达在早期显著增加。此外，在小鼠模型中证实了聚肌苷酸-聚胞苷酸-脂质体对生长的抑制作用。综上所述，这些结果表明聚肌苷酸-聚胞苷酸-脂质体可作为肝癌细胞中一种潜在的凋亡诱导剂，并暗示了一种潜在的治疗策略。
