褪黑激素抑制口腔癌細胞轉移之機制探討

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褪黑激素抑制口腔癌细胞转移之机制探讨

Study of the inhibitory effects of melatonin on the metastasis of oral cancer cells

叶家铭 , 博士　　导师：杨顺发　　

繁体中文

褪黑激素；转录辅助活化因子；组织蛋白乙醯化；基质金属蛋白水解酶； melatonin ； CREBBP ； EP300 ； Histone acetylation ； matrix metalloproteinase

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摘要 │ 参考文献 (120) │ 国际计量

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Melatonin exerts antimetastatic effects on liver and breast cancer and also inhibits matrix metalloproteinase (MMP) activity. However, the detailed impacts and underlying mechanisms of melatonin on oral cancer cell metastasis are still unclear. This study showed that melatonin attenuated the 12-O-tetradecanoylphorbol-13-acetate-induced migration of oral cancer cell lines, HSC-3 and OECM-1. Zymography, quantitative real-time PCR, and Western blotting analyses revealed that melatonin lessened MMP-9 enzyme activity as well as the expression of MMP-9 mRNA and protein. Furthermore, melatonin suppressed the phosphorylation of the ERK1/2 signalling pathway, which dampened MMP-9 gene transcription by affecting the expression of transcriptional coactivators, such as CREB-binding protein (CREBBP) and E1A binding protein p300 (EP300), and decreasing histone acetylation in HSC-3 and OECM-1 cells. Examinations on clinical samples exhibited that MMP-9, CREBBP, and EP300 were significantly increased in oral cancer tissues. Moreover, the relative level of CREBBP was positively correlated with the expression of MMP-9 and EP300. In conclusion, we demonstrated that melatonin inhibits the motility of HSC-3 and OECM-1 cells in vitro through a molecular mechanism that involves attenuation of MMP-9 expression and activity mediated by decreased histone acetylation.

参考文献 ( 120 ) 〈TOP〉

Adler, V., Franklin, C.C., Kraft, A.S., 1992. Phorbol esters stimulate the phosphorylation of c-Jun but not v-Jun: regulation by the N-terminal delta domain. Proceedings of the National Academy of Sciences of the United States of America 89, 5341-5345.
连结：
Al-Mehdi, A.B., Tozawa, K., Fisher, A.B., Shientag, L., Lee, A., Muschel, R.J., 2000. Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nature medicine 6, 100-102.
连结：
Albanese, C., D'Amico, M., Reutens, A.T., Fu, M., Watanabe, G., Lee, R.J., Kitsis, R.N., Henglein, B., Avantaggiati, M., Somasundaram, K., Thimmapaya, B., Pestell, R.G., 1999. Activation of the cyclin D1 gene by the E1A-associated protein p300 through AP-1 inhibits cellular apoptosis. The Journal of biological chemistry 274, 34186-34195.
连结：
Allfrey, V.G., Faulkner, R., Mirsky, A.E., 1964. ACETYLATION AND METHYLATION OF HISTONES AND THEIR POSSIBLE ROLE IN THE REGULATION OF RNA SYNTHESIS. Proceedings of the National Academy of Sciences of the United States of America 51, 786-794.
连结：
Bae, J.Y., Choi, J.S., Choi, Y.J., Shin, S.Y., Kang, S.W., Han, S.J., Kang, Y.H., 2008. (-)Epigallocatechin gallate hampers collagen destruction and collagenase activation in ultraviolet-B-irradiated human dermal fibroblasts: involvement of mitogen-activated protein kinase. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 46, 1298-1307.
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使用DOI作为永久连结

引用含有DOI的文献

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。 如想对DOI的使用与概念有进一步了解，请参考 （ ） 。

DOI可强化引用精确性、增强学术圈连结，并给予使用者跨平台的良好使用经验，目前在全世界已有超过五千万个对象申请DOI。如想对DOI的使用与概念有进一步了解，请参考（）。