| 摘要: | 本論文主要是探討綠茶唲茶素（GTCs），特別是（-）-表沒食子酸酯型唲茶素酸酯（英文名epigallocatechin gallate；簡稱 EGCG）對人類胎盤滋養層生長的影響。第一章研究EGCG是否對人類胎盤絨毛膜癌細胞生長具有抑制作用。我們以BeWo，JEG-3和JAR等胎盤絨毛膜癌細胞株為研究素材，結果發現EGCG抑制胎盤絨毛膜癌細胞株增生，且具有時間效應與濃度效應。綠茶唲茶素中以EGCG對於抑制細胞生長作用較其他唲茶素(EC、ECG及EGC)為明顯。研究結果顯示EGCG透過AMPK，ERK，和p38等訊息路徑調控胎盤絨毛膜癌細胞的生長，而非JNK路徑。第二章探討EGCG是否會影響正常人類絨毛膜滋養層細胞的生長。研究顯示EGCG抑制細胞生長比其他唲茶素更為明顯。處理ERK1/2，p38及AMPK的抑制劑後，受EGCG誘導細胞數減少與BrdU嵌入的實驗產生拮抗作用，分別阻斷受EGCG刺激的MEK1、p38及AMPK等蛋白質的表現。而EGCG就類似於PI3K專一性抑制劑，具有抑制AKT磷酸化、細胞數及BrdU嵌入的作用。EGCG抑制HVT細胞的增生是透過ERK，P38，AMPK和AKT的路徑。其結論是EGCG在正常與癌變的絨毛滋養細胞之間可能具有相似或不同的抗增生作用機制。此論文結果說明於大量使用或長期食用EGCG，含有EGCG成分茶飲和民間藥物，是否會影響體內正常和癌變滋養層細胞的生長，值得討論。;The overall objective of this dissertation was to investigate the effects of green tea catechins (GTCs), especially epigallocatechin-3-gallate (EGCG), on the growth of human placental trophoblasts. The first chapter was to study whether EGCG induced growth inhibition of human placental choriocarcinoma cells. Using BeWo, JEG-3, and JAR choriocarcinoma cells, we discovered that EGCG suppressed the proliferation of all three of the choriocarcinoma cells in dose-dependent and time-dependent manners. A catechin-specific effect of green tea was evident; EGCG was more effective than epicatechin (EC), epicatechin gallate (ECG), and epigallocatechin (EGC) in suppressing cell growth. We found that EGCG suppressed choriocarcinoma cell growth via the AMPK, ERK, and p38 but not JNK pathways. The second chapter was to investigate whether EGCG affects mitogenesis in human villous trophoblasts (HVT). We discovered that EGCG was more effective than other GTCs in suppressing cell growth. Also, the specific inhibitors of ERK1/2, p38, or AMPK blocked EGCG-induced decreases in both cell number and bromodeoxyuridine (BrdU) incorporation, as well as respectively blocking EGCG-stimulated activities of MEK1, p38, and AMPK proteins. Moreover, EGCG was similar to the specific inhibitor of PI3K by inhibiting AKT phosphorylation, cell number and BrdU incorporation. These data imply that EGCG inhibits the growth of HVT through the ERK, p38, AMPK and AKT pathways. We concluded that EGCG acts as an anti-proliferative agent on both normal villous trophoblasts and cancerous trophoblasts can be similar through the ERK, P38, and AMPK pathways, and different through the PI3K/AKT pathways. |
