| Summary: | 碩士 === 國立陽明大學 === 口腔生物研究所 === 97 === Head and neck squamous cell carcinoma (HNSCC), including oral cancer, is the sixth most common types of human cancer. In South-Eastern Asia, alcohol, tobacco and areca nut abuse are main risk of carcinogenic factors. The five year survival rate of approximately 50% patients, particularly in stage III or IV, has not improved through surgery, radiotherapy or chemotherapy during decade. BO-1051 is a new 9-anilinoacridine N-mustard derivative and exhibits potential antitumor therapeutic efficacy in nude mice against human tumor xenogeafts. In this study, we found that treatment of BO-1051 in oral cancer cell lines induce significant cytotoxicity with low IC50 and cell cycle arrest. Data of up-regulated checkpoint kinases expression demonstrated that BO-1051 caused DNA damage and involved in mechanism of DNA repair. Our data also showed that the new compound could active autophagic cell death through expression of marked LC3II with time- and dose- dependent manner. However, BO-1051 might induce apoptosis over 24 hour by up-ragulated caspase 3 and PARP. It suggests that we have to examine the order of cell death-induced with autophagy inhibitors 3-MA or bafilomycin A1. On the other hand, we also found that BO-1051 could cause tumor growth delay, but not enhance the radiosensitivity of a SAS-derived xenograft. Together, these results suggest that BO-1051 may be a potential cancer agent combined with radiation for oral therapy.
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