數種天然藥物之純化成分對人類肝癌細胞增生抑制作用和細胞程式死亡機制之探討

The proliferative inhibition and apoptotic mechanism of several natural products in human hepatoma cells

郭柏麟(Po-Lin Kuo)

指導教授 ： 林俊清

高雄醫學大學/藥學院/天然藥物研究所碩士班/博士(2004年)

摘要

肝癌是世界上最常見惡性腫瘤之一，根據世界衛生組織的統計，每年有超過一百萬人死於此疾病；在台灣，依據我國官方的統計資料也顯示每年約有五千多人死於肝癌。所以，開發一有效且安全的抗肝癌藥物乃為當務之急。
本研究目標乃從天然藥物中分別將其純化成份深入地探索其抗肝癌之活性機轉。經過初步的活性篩選結果中發現aloe-emodin、resveratrol、EGCG ((-)-epigallocatechin-3-gallate)、tetrandrine及rhein等能有效地抑制肝癌細胞增生作用；因此接續以這些純化成分單獨針對受測細胞株p53-positive Hep G2或者亦和p53-deficient Hep 3B進行抗肝癌活性研究並建立其相關的機轉。
整體研究分成三大步驟，第一是初步抗癌活性的建立，確認抑制癌細胞增生所需之有效抑制濃度，分別確認藥物濃度和作用時間與其效應的關係性，並初步地探討抑制癌細胞增生的狀況，包括細胞凋亡及細胞週期停止等等。第二則針對藥物對腫瘤細胞抑制其增生之機轉確立，評估該純化成分對p53、p21、Fas receptor和Fas ligand的影響。最後則企圖更深入地從另一途徑來瞭解活性成分的分子生物機轉，包括Bcl-2及Bax等，並藉由比較不同基因背景的肝癌細胞株來確認這些受影響的分子是否透過p53所主導，建立其抗肝癌途徑。

關鍵字

蘆薈大黃苷白藜蘆醇 ； 綠茶兒茶素 ； 粉防己鹹 ； 氧化大黃苷細胞凋亡 ； 細胞週期 ； p53

並列摘要

Hepatocellular carcinoma (HCC) is one of the most lethal malignancies, and is also one of the four most prevalent malignant diseases of adults in China, Taiwan, Korea, and Sub-Africa.
This research project was divided into three portions. For the first step, we plan to assay the antiproliferative effects of aloe-emodin, resveratrol, EGCG ((-)-epigallocatechin-3-gallate), tetrandrine and rhein in two human liver cancer cell lines, Hep G2 and Hep 3B, and determine the time- and dose-dependent responses. We also examined these compounds, for the study of their impacts on cell growth and cell cycle progression. For the second and third steps, to provide a better understanding of the anticancer effect in molecular basis, we assayed several target molecules such as p53, p21, Fas ligand, Fas receptor, Bcl-2, Bax, which were strongly associated with apoptotic pathway and were believed having something to do with the chemosensitivity’s efficacies upon anticancer drug therapy.

並列關鍵字

aloe-emodin ； resveratrol ； EGCG ； tetrandrine ； rhein ； apoptosis ； cell cycle ； p53

參考文獻

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