| Summary: | 碩士 === 國立中興大學 === 生物醫學研究所 === 105 === Cellular senescence is a permanent cell growth arrest, and thought a strategy to prevent tumors in vivo. Imiquimod (IMQ) is a ligand of toll-like receptor 7/8 (TLR7/8), contains anti-tumor and anti-viral activity in vitro and in vivo. In our previous studies we had demonstrated IMQ induced autophagy and apoptosis in dental doses, but low dose IMQ induced human basal cell carcinomas (BCC) growth arrested and change of morphology. That the characteristic of senescence. Here, we investigated low dose of IMQ (10μg/ml) induced p53-wildtype BCC into senescence. Although, in p53-mutant and p53-knockdown skin cancer cells IMQ might just induce G1 phase arrested and this should have more discussion. We found the role of IMQ-induced senescence in BCC model had interaction with IMQ-induced autophagy. Interruption of autophagy by autophagy inhibitors could also reduce IMQ-induced senescence. Interleukin-6 (IL-6) is an important cytokine of senescence-associated secretory phenotype (SASP). The blockage of IL-6 could reduce IMQ-induced senescence and autophagy. Reactive oxygen species (ROS) induced senescence through DNA damage response (DDR) to activated ATM/ATR pathway was reported. In our study, we eliminated ROS in BCC reduced IMQ-induced senescence. We considered these findings could be useful to basic research and clinical application of IMQ in future.
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