四物湯為傳統中草藥，在亞洲地區廣泛應用於女性調經與紓緩經痛。近年有研究證實長期使用四物湯可有效的減輕經期不適，且無不良副作用產生。因此本論文對四物湯做進一步的探討，從基因體方面研究四物湯對於兩種常見婦科疾病子宮內膜異位症以及卵巢癌的作用。生物活性測試結果顯示，四物湯水萃物具有抑制SKOV-3卵巢癌細胞株以及人類子宮內膜異位基質細胞的生長作用。另一方面，利用生物反應指紋分析技術，顯示四物湯水萃物處理後的基因圖譜具有高植物相似度指數(PSI > 0.95)，確定四物湯水萃物品質的一致性。進一步以生物資訊學分析四物湯水萃物作用的細胞路徑並加以驗證，結果顯示四物湯水萃物可調控AP-1 (Activating protein-1)路徑或是HER2/PI3K/Akt路徑而影響卵巢癌細胞株的生長，亦可調控APC (Anaphase promoting complex)路徑而抑制人類子宮內膜異位基質細胞的細胞週期。目標希望能找到四物湯影響子宮內膜異位以及卵巢癌細胞增生的可能機制，提供未來臨床上以中草藥治療此方面疾病的輔助療法。
Four-Agents-Decoction (FAD; also known as Si-Wu-Tang), has been widely used for regulating menstruation and relieving pains for centuries in Asian countries. Recent studies show that long-term use of FAD does effectively reduce dysmenorrhea without any side-effects. To further unravel the underlying effects of FAD on gynecological disorders, e.g., endometriosis and ovarian cancer, a systematic genomic profiling approach was used in this study. Based on the biological assay, the FAD extract (FADE) revealed an anti-proliferation effect on primary human endometrosis cells and ovarian cancer cells. Furthermore, the Genomic Bioresponse Fingerprint analyses on both of the FADE-treated endometrosis cells and ovarian cancer cells demonstrate high Phytomics Similarity Index (PSI > 0.95), showing high quality of FADE. In addition, possible FADE-mediated cellular networks were obtained through bioinformatics analysis. The results reveal that the AP-1 (Activating protein-1) pathway and ERBB2/PI3K/AKT pathway are involved in FADE-treated SKOV-3 cells, and the cell cycle-related APC (Anaphase promoting complex) pathway is affected by FADE in endometriosis stromal cells. Validation for these cellular pathways is further performed. The final goal of this study is to unravel possible mechanisms of anti-proliferation effects on endometrosis and ovarian cancer cells by FADE, and provide an alternative method for the treatment of endometriosis and ovarian cancer.
