| Summary: | 碩士 === 國立高雄師範大學 === 生物科技系 === 99 === Cancer is the leading cause of death in recent year. Environmental or occupational carcinogen exposure is closely related to cancer occurrences. It has been reported that overexposure of biphenyl amine compounds contained in smoke and azo-dyes is related to bladder cancer occurrence. However, the molecular mechanisms of biphenyl amine compounds-induced bladder cancer are still unclear. Many studies have demonstrated that overexpression of cyclooxygenase-2 (COX-2) in neoplastic lesions is associated with carcinogenesis. Whether the biphenyl amine compounds could regulate the expression of COX-2 was investigated in this study. The signaling pathways of biphenyl amine compound-induced COX-2 expression in human bladder cancer cell lines TSGH-8301 cells were further examined. We found that 2-Aminobiphenyl (2-ABP) could induce COX-2 expression in a dose- and time-dependent manner. The reactive oxygen species production (ROS) production, phosphorylation of mitogen-activated protein kinase, ERK and JNK, and activation of transcription factor c-Jun, ATF-2 were enhanced by 2-ABP treatment. Moreover, 2-ABP induced COX-2 expression, ERK/JNK and c-Jun, ATF-2 phosphorylation were significantly inhibited by JNK inhibitor (SP600125) and ERK1/2 inhibitor (U0126). The ROS scavenger, N-acetyl cysteine (NAC), also could attenuate 2-ABP-induced COX-2 expression and c-Jun, ATF-2 phosphorylation. Furthermore, we found that NADPH oxidase inhibitor (apocynin) also has the same inhibitory effects on 2-ABP-induced COX-2 expression and c-Jun, ATF-2 phosphorylation. Stimulation of 2-ABP was also found to induce the expression of NADPH oxidase subunit p22. These results indicated that 2-ABP induces COX-2 expression mediated through NADPH oxidase stimulated ROS production and JNK/ERK activation, which is regulated by transcription factors c-Jun and ATF-2.
|
|---|
