黃芩素抑制神經膠原致癌基因表現及對於卵巢癌細胞之抑癌活性的分子機轉探討

淡江大學機構典藏 > 理學院 > 化學學系暨研究所 > 研究報告 > Item 987654321/76125

請使用永久網址來引用或連結此文件: https://tkuir.lib.tku.edu.tw/dspace/handle/987654321/76125

題名:	黃芩素抑制神經膠原致癌基因表現及對於卵巢癌細胞之抑癌活性的分子機轉探討
其他題名:	Molecular Mechanisms of Her2 Suppression and Antitumor Activity by Baicalein on Ovarian Cancer Cells: in Vitro and in Vivo.
作者:	莊子超;李守倫
貢獻者:	淡江大學化學學系
關鍵詞:	神經膠原致癌基因;卵巢癌;黃芩素;黃芩
日期:	2011-08
上傳時間:	2012-05-02 09:50:41 (UTC+8)
摘要:	在人類約有2‐35 % 的卵巢癌病人及其他癌症病例有神經膠原致癌基因(HER2)倍增及其蛋白質(p185HER2) 過度表現的情形且預後不佳，所以HER2 基因是一重要的治療標靶分子。雖已有研究顯示黃芩素在數種癌細胞上有抗癌細胞增生及促進癌細胞凋亡的效果，我們初步的實驗首度證實黃芩素不僅可抑制p185HER2 過表現癌細胞的增生，並可抑制HER2 的基因表現(實驗附圖1‐2, 5)。已初步鎖定了黃芩素作用在p185HER2 過表現之癌細胞中對p185HER2 及其下游生長訊號分子、癌細胞轉移分子的影響來進行分析(實驗附圖3‐4)。然而黃芩素造成p185HER2 抑制的分子機制及在p185HER2 過表現卵巢癌細胞中的影響還待進一步探討。為能清楚明瞭這其中的作用機制，我們提出了這個計畫。此計畫的六個目標為：第一年計畫一、探討黃芩素是否能藉由抑制HER2 致癌基因的表現，因而降低p185HER2 過度表現所造成的卵巢癌細胞之細胞轉形、血管增生及抗藥性？二、探討黃芩素作用在p185HER2 過表現的卵巢癌細胞中抑制HER2 基因表現的分子機制？第二年計畫三、探討黃芩素作用在過表現p185HER2 的卵巢癌細胞中，可否藉由抑制HER2 的基因表現進而促進癌細胞凋亡、細胞自噬死亡或細胞自噬？四、探討黃芩素造成多種卵巢癌細胞，細胞週期G2/M 停滯的分子機制？第三年計畫五、探討黃芩素作用在卵巢癌、乳癌、子宮頸癌細胞中，可否引發細胞自噬? 抑制細胞自噬是否可促進黃芩素在過表現p185HER2 卵巢癌等癌細胞之凋亡現象? 六、藉由植入p185HER2 過表現卵巢癌細胞的裸鼠及/或改良過的Tsukamoto‐French 動物模式來證實與評估黃芩素對p185HER2 過表現卵巢癌細胞的療效：抑制p185HER2 表現、抗腫瘤及生物毒性。 HER2 oncogene is known to be amplified and/or over‐expressed in approximately 2‐35% of human ovarian cancer patients as well as many other cancers, and poor response to treatment. Given its role in poor prognosis, p185HER2 is considered as an important molecular target in ovarian and breast cancers. Previous studies have shown the anti‐proliferative and pro‐apoptotic effects of baicalein in several cancer cells. Using several human ovarian and breast cancer cell lines as experimental materials, our preliminary results showed here for the first time that baicalein not only inhibit the survival rate of p185HER2‐overexpressing cells, but also inhibit p185HER2 expression in ovary and breast cancer cells (Figure 1‐2,5). However, the molecular mechanism of action of baicalein has not been investigated in p185HER2‐overexpressing cancer cells. Therefore, we investigated the effects of baicalein on HER2/PI3K/Akt signaling pathway, and other metastatic association molecules in p185HER2‐overexprrssing cancer cells (Figure 3‐4). The molecular mechanisms of baicalein‐induced p185HER2 suppression, effects of baicalein in p185HER2‐overexpressing cancer cells remain to be elucidated. In order to better understand the mechanisms involved, we launch this proposal. The six specific aims of this proposal are: 1st year project (1) To know whether the baicalein is capable of suppressing the p185HER2‐mediated transformation, metastatic potential, angiogenesis and chemotherapeutic resistance in ovary and breast cancer cells. (2) To investigate the underlying molecular mechanism of suppression of HER2 oncogene expression by baicalein in p185HER2‐overexpressing human ovary and breast cancers. 2nd year project (3) To evaluate the effects, including inducing apoptosis, autophage and autophagic cell death, of suppression of p185HER2 expression by baicalein in p185HER2‐overexpressing human ovary and breast cancers. (4) To investigate the underlying molecular mechanism of causing G2/M arrest by baicalein in several human ovary cancers. 3rd year project (5) To analyze whether baicalein could induce autophage, and whether autophage inhibition could enhance baicalein‐induced apoptosis in p185HER2‐overexpressing human ovary and breast cancers. (6) To determine the antiproliferative and chemopreventive effects of baicalein in human p185HER2‐overexpressing cancer cells by using tumor‐bearing nude mice and/or modified Tsukamoto‐French animal models.
顯示於類別:	[化學學系暨研究所] 研究報告

文件中的檔案:

沒有與此文件相關的檔案.

在機構典藏中所有的資料項目都受到原著作權保護.

TAIR相關文章

資料載入中.....