| Summary: | 碩士 === 國立中興大學 === 醫學科技研究所 === 97 === Imiquimod（1-isobutyl-1H-imidazo[4,5-c]quinolin-4-amine), an immune response modifier, has potent antitumor activity. Imiquimod induces local production of cytokines through the interaction with Toll-like receptor 7 on immune cells. It shows clinical efficacy against several benign and malignant skin lesions, including actinic keratosis and basal cell carcinoma. In addition to the effects of immune modulation, imiquimod had been reported to possess considerable proapopotic activity against melanoma cells, mediated through Bcl-2-dependent release mitochondrial cytochrome c and subsequent activation of caspase 3 and caspase 9. In this study, we examined the imiquimod-induced cell death in different cancer cell lines. We discovered that imiquimod induced cell apoptosis and decreased the level of anti-apoptotic proteins in AGS and HepG2 cells. However, the percentage of sub-G1 cells showed no significant difference in A549 and T24 cells after imiquimod treatment. We show here that apoptosis is not the only mechanism of cell death caused by imiquimod. Autophagy may be a mechanism of stress-adaption by which the cell is trying to survive. We observed that imiquimod induce autophagy, indicated by LC3-I converted to LC3-II and developed cytoplasmic acridic orange (AO) AO puncta in A549 and T24 cells. In addition, imiquimod induced caspase 3 activetion in A549. Taken together, we observed that imiquimod induce both autophagy and apoptosis in A549 cells. However, only autophagy is significantly increased in the T24 upon imiquimod insults. Thus, the imiquimod may have differential effects on different cancer cell lines, and autophagy may be an important protective mechanism in specific cancer cells which have the ability to resistant imiquimod-induced apoptosis.
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