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  • 學位論文

3,3'-二吲哚甲烷抑制神經膠原致癌基因表現和轉移特性之研究

Suppression of HER2/neu expression and its metastasis by 3,3'-Diindolylmethane

指導教授 : 莊子超

摘要


在人類乳癌和其它的癌症病患中約有 30~40% 肇因於神經膠原致癌基因大放大或過度表現。3,3'-二吲哚甲烷 (DIM) 為吲哚三甲醇 (I3C) 在酸性條件下所形成的雙聚體, 和 I3C 比起來,DIM 具有較穩定且較好的抗癌效果。 從最近的文獻得之 3,3'-二吲哚甲烷對於不同的癌細胞有抗增生和促進細胞凋亡的功能。在本研究中,我們首先證實 3,3'-二吲哚甲烷可抑制神經膠原致癌基因的表現。再者,更發現 3,3'-二吲哚甲烷對於神經膠原致癌基因過度表現的癌細胞,不僅能有效抑制癌細胞的存活率及降低內生性p185HER2/neu的表現,也可抑制因神經膠原致癌基因所引發的細胞癌變和轉移能力。 這些結果證實3,3'-二吲哚甲烷可做為對抗神經膠原致癌基因的標靶抗癌藥物。 關鍵字:神經膠原致癌基因、3,3'-二吲哚甲烷、轉移

並列摘要


HER2/neu oncogene is known to be amplified and/or over-expressed in approximately 30-40% of human breast cancers and many other cancers. And, 3,3’-Diindolylmethane (DIM) is a dimer of indole-3-carbinol (I3C) that is formed under acidic conditions and unlike I3C is more stable with higher anti-cancer effects. Previous studies have shown the antiproliferative and proapoptotic effects of DIM in several cancer cells. In the present study, we demonstrated for the first time that DIM suppresses the HER2/neu oncogene expression. Furthermore, we also found DIM could inhibit the survival rate and downregulate the endogenous production of p185HER2/neu of HER2/neu-overexpressing cancer cells, as well as suppress the HER2/neu-mediated transformation and metastatic potential. These data suggest that DIM may act as a HER2/neu-targeting anticancer drug.

並列關鍵字

HER2/neu DIM Metastasis

參考文獻


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Anderton, M.J., Jukes, R., Lamb, J.H., Manson, M.M., Gescher, A., Steward, W.P. & Williams, M.L. (2003) Liquid chromatographic assay for the simultaneous determination of indole-3-carbinol and its acid condensation products in plasma. J Chromatogr B Analyt Technol Biomed Life Sci 787(2), 281-91.
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