| 摘要: | 中醫方藥全基因體基因表現圖譜
資料庫之建構及其應用
研究生：鄭文裕
指導教授：侯庭鏞博士
中國醫藥大學：中國醫學研究所
目的: 本研究之目標是建構中醫方藥全基因體基因表現圖譜資料庫，並應用於新藥篩選與開發。
材料與方法:分別以15複方、三黃瀉心湯及其組成(黃芩、黃連、大黃)、香草醛及quinoclamine處理 HepG2細胞，然後以微陣列分析基因表現圖譜。
結果：第一：中藥15複方在毒性相關基因表現上與EDGE資料
庫裡的化合物呈現不同的圖譜結果，據此我們認為中藥15個複方處理至實驗動物體內於腎臟中的代謝是無害的。第二：三黃瀉心湯具有促牽涉到p53的訊息傳導、p53基因的活化以及DNA damage訊息傳遞的基因表現之調節，而且此調節與抗細胞增殖有關；此研究結果與臨床應用上相呼應。另外，黃連在三黃瀉心湯中具有主要作用。第三：被香草醛下調的基因關聯到細胞增殖、細胞週期、細胞凋亡以及腫瘤的發展；並且此調節牽涉到對核心分子activator protein(AP-1)的抑制；而且，香草醛主要是藉由extracellular signal-regulated kinases (ERKs)訊息傳遞路徑來抑制AP-1的活性。第四：quinoclamine是nuclear factor-κB (NF-κB)的抑制劑，能夠藉由調節細胞週期與促細胞凋亡而具抗癌的潛能；而且quinoclamine藉由下調部分UGT的相關基因，進而干擾藥物的代謝速率，延長藥物在體內的作用時間，而更提高其抗癌的潛能。
結論：研究結果顯示中醫方藥全基因體基因表現圖譜資料庫之建構及應用於新藥篩選及開發是很有前景的。
Construction and Application of Whole
Genome Expression Profile Database for
Chinese Medicinal Herbs
Wen-Yu Cheng
Adviser: Tin-Yun Ho
Graduate Institute of Chinese Medical Science, China Medical University
PURPOPSE: The objective of this study is to construct the whole genome expression profile database for Chinese medicinal herbs and its application on the virtual screening of new drug development.
METHODS AND MATERIALS: HepG2 cells were treated with 15 formulae, SHXXT and its components, vanillin, and quinoclamine, and the gene expression profiles were analyzed by DNA microarray.
RESULTS: Firstly, our results showed that formulae displayed different expression profiles of the toxicology-related genes with chemicals, suggesting that the toxicities of 15 formula treatments in kidney might be ignored. Secondly, gene set enrichment analysis indicated that SHXXT and its components displayed a unique antiproliferation pattern via p53 signaling, activated, and DNA damage signaling pathways in HepG2 cells. Network analysis showed that most genes were regulated by p53. Thirdly, genes down-regulated by vanillin were associated with cellular process, cell cycle, death, and cancer progression. Fos may play a central role in the regulation of the gene expression network. Analysis of Fos-related transcription factor, activator protein 1 (AP-1), showed that vanillin inhibited AP-1 activity in a dose-dependent manner. Furthermore, vanillin regulated AP-1 activity via extracellular signal-regulated protein kinase pathway. Finally, quinoclamine-regulated genes interacted with nuclear factor-κB or its downstream genes by network analysis. Moreover, these genes were involved in cell cycle and apoptosis by gene ontology annotation.
CONCLUSION: The results of this study showed a perspective of constructing the whole genome gene expression profiles database for Chinese medicinal herbs and its application on the virtual screening of new drug development. |
