| 摘要: | 肺癌在全世界是最常見且死亡率最高的癌症，在台灣也不例外。許多的病人由於肺腺癌的高轉移性而常常在診斷後被發現已經是癌症晚期。就算病人在診斷後為初期就動手術把腫瘤切除，肺腺癌往往會在數個月後轉移復發並且伴隨著高死亡率，這也是肺癌死亡率居高不下的原因。近年來艾瑞莎(Gefitinib)及得舒緩(Erlotinib)是肺癌最常被使用的標靶藥物，但是兩者都沒有抑制肺腺癌細胞轉移的效果，因此尋找一種全新的藥物來針對抑制肺腺癌的轉移是十分重要的。在我們的研究中，我們想要找到一種中國傳統中藥並且具有抑制肺腺癌細胞爬行及轉移的功能，因為中國傳統中藥相對於化學療法及放射療法有許多的優點，像是低副作用、天然、低毒性、便宜等。在經過細胞學實驗的驗證後，我們發現150 μg/ml濃度的BP011w顯著的抑制CL1-5細胞株的爬行及轉移，經由微陣列基因晶片資料的分析後，我們找到了四個候選基因DYNAP、FGF16、miR-548L及REN。在微陣列基因晶片的資料中，DYNAP、FGF16B及REN在BP011w的藥物處理之後基因為下表現，而MIR-548L則為上表現。DYNAP、FGF16B是和PI3K/AKT路徑相關，FGF16B、REN則是和RAS/ERK路徑相關。最後，我們推測是由於BP011w造成這四個基因表現的變化而導致PI3K/AKT及RAS/ERK的下游訊號被阻擋進而造成抑制肺腺癌細胞株的爬行及轉移。;Lung cancer is one of the most frequently diagnosed cancers and is the major cause of cancer-related death worldwide, as well as in Taiwan. Most patients were diagnosed with advanced-stage lung adenocarcinomas because of its highly metastatic rate. Even if diagnosed at an early stage and surgically removed, lung adenocarcinomas can recurrence and extending to other organs with a high mortality rate after a few months. Recently, Gefitinib and Erlotinib were the most common target therapy for lung cancer, but both of them can’t inhibit the cell migration. Therefore, it is necessary to find a brand new drug against to the metastatic of lung cancer, especially for lung adenocarcinoma. In our study, we want to search a Traditional Chinese Medicines to inhibit cell migration of lung adenocarcinoma because TCMs have lots of advantages including less side effects, naturally, low toxicity, inexpensive than chemotherapy and radiotherapy. After identify by cytological analysis, we found the dosage of 150 μg/ml BP011w could inhibit CL1-5 migration obviously. After analysis the data of microarray, we found 4 candidate genes, DYNAP, FGF16, MIR-548L and REN. In the microarray data, DYNAP, FGF16 and REN were down-regulated; miR-548L was up-regulated after treating by BP011w. DYNAP and MIR-548L were related to PI3K/AKT pathway, FGF16 and REN were related to RAS/ERK pathway. Finally, we surmised that the change of 4 gene expression could block the downstream signal of PI3K/AKT and RAS/ERK due to the treatment of BP011w. |
