| 摘要: | Activator protein 1 (AP-1)為一種轉錄因子，可調控細胞的分裂、分化及轉形，而阻斷AP-1的活性也可抑制細胞的轉形，因此本研究主要就以AP-1為標的開發抗肝細胞轉形藥物。實驗是先利用經12-O-tetradecanoylphorbol-13-acetate (TPA)處理的Chang/AP-1及HepG2/AP-1重組細胞為材料，偵測98種中藥對細胞AP-1活性的影響。再從中篩選出抑制AP-1效果最好的10種中藥，分別是麻黃、吳茱萸、厚朴、大黃、檳榔、防己、知母、皂莢、苦參、甘草。進一步測試這10種中藥在抑制AP-1活性、細胞毒殺效應及肝細胞轉形的能力，其中對吳茱萸的甲醇萃取物、酸性乙醇及乙醇萃取物效果最佳，而且這些效應呈現劑量反應。因此由本研究的結果顯示，藉由中藥對AP-1活性的影響，可快速篩選出具有抗肝細胞轉形潛能的中藥，而本研究所篩選出的吳茱萸，在體外試驗中皆呈現明顯的抗肝細胞轉形效應，因此值得進一步利用動物試驗驗證其治療肝癌的效果。; Activator protein 1(AP-1), a nuclear transcription factor, plays important roles in cell proliferation, differentiation, and transformation. Previous study indicated that blocking of AP-1 activity is able to inhibit the cellular transformation. We therefore develop the anti-human hepatocellular compounds using AP-1 on the target in this study. Effects of 98 herbs on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced AP-1 activity in Chang/AP-1 and HepG2/AP-1 recombinant cells were investigated. Among the herbs, 10 herbs, which showed inhibition abilities on AP-1 activity, were selected. These herbs include Ephedra sinica, Evodia rutaecarpa, Magnolia officinallis, Rheum officinale, Arcea catechu, Stephanica tetrandra, Anemarrhena asphodeloids, Gledititsia sinensis, Sophora flavescens, and Glycyrrhiza uralensis. These herbs were further analyzed for their anti-AP-1 activities and anti-hepatocellular transformation activities by luciferase assay and anchorage-independent transformation assay. Results showed that Evodia rutaecarpa exhibited the significant inhibition ability on AP-1 activity and hepatocellular transformation in a dose-dependent manner. Moreover, the methanol, acid alcoholic, and alcoholic extracts of E. rutaecarpa were responsible for their anti-hepatocellular transformation abilities. |
