| Summary: | 碩士 === 國立成功大學 === 醫學檢驗生物技術學系碩博士班 === 98 === Arsenic existed ubiquitously in the environment in both inorganic and organic forms. Epidemiological studies had identified an increased risk of various tumors, including those of the skin, lung, liver and urinary tract, when chronic exposure to arsenic. However, arsenic had also been used to treat a number of diseases for more than 2400 years. Especially, arsenic trioxide (ATO) can be effectively used to treat acute promyelocytic leukemia, and some other solid tumors. The mechanisms of the carcinogenic and therapeutic effects of arsenic were still poorly understood, and should be further elucidated for therapeutic purposes. Previously, we found that low-level ATO increased cellular proliferation, while high-level ATO induced cellular toxicity in keratinocytes. To further investigate the role of low-level ATO in the carcinogenesis, we exposure HaCaT (transformed human keratinocyte cell line) cells with low-level ATO for a long period. We found that chronic treatment with low-level ATO to HaCaT could increase cellular proliferation, migration, invasion, MMP-9, ROS, TGIF, and p-EGFR(Y845) expression. Moreover, cells migration ability was largely reduced after inhibit MMPs, superoxide, and TGIF in long-term ATO exposure cells. Besides, TGIF was involved in arsenic trioxide-induced p-EGFR(Y845) expression. On the other hand, interruption of ATO supply in long-term ATO exposure cells did not restore cell viability, cell migration and phosphorylation of EGFR to control cells level, it might because cells signaling were irreversibly altered after long-term of ATO exposure. In addition, low dose ATO exposure also affected breast cancer cell (MCF-7) and hepatoma cell line (Huh-7) proliferation and increased MCF-7 cell migration ability, indicated that chronic low dose exposure of ATO might have carcinogenic effect not only in keratinocytes but also in breast cancer cells, and hepatoma cells. Overall, in this study, the mechanisms that involved in arsenic trioxide induced-carcinogenesis might give us hints in clinical application.
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