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    Title: 厚朴酚抑制神經膠原致癌基因表現及癌細胞轉移
    Other Titles: Magnolol suppresses HER2/neu expression and its mediated metastasis
    Authors: 鄭逸婷;Cheng, Yi-ting
    Contributors: 淡江大學化學學系碩士班
    莊子超;Chuang, Tzu-chao
    Keywords: 厚朴酚;神經膠原致癌基因;細胞轉移;Magnolol;p185HER2/neu;Metastasis
    Date: 2008
    Issue Date: 2010-01-11 02:33:16 (UTC+8)
    Abstract: p185HER2/neu 是一種致癌基因,p185HER2/neu 的過度表現與癌細胞的生長息息相關,在乳癌中 p185HER2/neu 的過度表現會增加癌細胞的轉移能力和減低預後情形。厚朴酚是從中藥厚朴 (Magnolia officinalis) 萃取出來的有效成分,至今已經發現有許多的藥理作用,例如:抗腫瘤、抗氧化及抗發炎。不過厚朴酚對 p185HER2/neu 過度表現癌細胞的效果還不清楚。在這裡,我們利用不同劑量和時間的方式,證明了厚朴酚可以誘導 p185HER2/neu 過度表現的癌細胞進行死亡。也發現厚朴酚可以抑制 HER2/neu 基因表現。我們也說明了厚朴酚可以降低 MMP2 的活性,再加入 EGF 之後又恢復了 MMP2 的活性。此外,LY294002 (PI3K 的抑制劑),也經由 EGF 恢復了 MMP2 的活性。這些發現證明厚朴酚可以有效抑制 p185HER2/neu 的過度表現和部份經由 PI3K/Akt 途徑降低 p185HER2/neu 過度表現所媒介的癌細胞轉移。總論,相同的我們發現厚朴酚在 p185HER2/neu 過度表現的卵巢癌細胞中也具有抑制轉移性質的相關功能。
    The oncoprotein HER2/neu is know to be overexpressed in several human cancers and it is associated with increased metastasis and poor prognosis. Magnolol, an active component extracted from Magnolia officinalis, has shown several pharmacological activities such as anti-tumor, anti-oxidant and anti-inflammatory effects. However, the effects of magnolol on the HER2/neu-overexpressing cancer cells are unknown. Here, we demonstrated that magnolol induced HER2/neu-overexpressing cancer cell death, in a dose- and time-dependent manner. We also reveled that magnolol could suppress the HER2/neu gene expression. We also elucidate that EGF specifically restores the activation of MMP2 after its activity was reduced by magnolol. Furthermore, LY294002, a PI3K inhibitor, attenuated the restoration of MMP2 activity by EGF. These finding suggest that magnolol can suppress HER2/neu expression, and then inhibiting the PI3K/Akt-signaling pathway to attenuate the p185HER2/neu mediated metastasis. Taken together, we found that magnolol is potent in suppressing metastasis-associated properties of HER2/neu-overexpressing ovarian cancer cells.
    Appears in Collections:[Graduate Institute & Department of Chemistry] Thesis

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