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CCMP95-RD-205 利用基因體啟動子體內外活性測定建立治療肺癌之中草藥萃取物篩選平台 (3-1)

  • 資料來源:中醫藥司
  • 建檔日期:95-12-30
  • 更新時間:109-02-18

利用基因體啟動子體內外活性測定建立治療肺癌之中草藥萃取物篩選平台 (3-1)

吳昭良
國立成功大學醫學院
癌症對生命的威脅很大,是疾病導致死亡的頭號殺手。在台灣肺癌的發生率及致死率又居高不下,同時肺癌細胞也容易擴散轉移到身體的其它器官,通常症狀出現才知道罹患肺癌,且在台灣肺癌病患常合併出現惡性肋膜積水,對於預防及診斷治療上有其困難。儘管醫學已有相當進展,但對於肺癌及其轉移的治療成果還是非常令人失望。所以近幾年肺癌治療迫切需要的是發展出抑制肺腫瘤細胞生長並且抑制其轉移的藥物,以提高治療效果,並且降低副作用的產生。然而許多相關報導指出傳統中草藥,不僅僅對於某些慢性疾病有治療效果,對於各種癌症的治療也有明顯的療效。可惜大部分由於之前沒有嚴謹臨床試驗的檢驗評估,多半的中草藥方缺乏科學的確切佐證,也極少有客觀的科學評估。所以本計畫利用已知癌細胞過度活化之啟動子(promoter)攜帶報告基因(luciferase),造就一篩選平台,希望利用快速、簡單的篩選機制,選殖出適合治療肺癌的中草藥。並且同時利用癌細胞毒殺實驗及轉移實驗測試中草藥對於肺癌細胞毒殺及惡性轉移的能力,並進一步探討其中中草藥對於抑制肺癌細胞生長及轉移訊息傳討之機制。而腫瘤生長,常伴隨著不正常的血管新生的現象,這樣的一個現象,對於原位腫瘤的生長及惡性轉移的情況有密切的關係,所以同時期待利用細胞篩選平台的方式能找出可以抑制腫瘤血管新生之中草藥。然而腫瘤於生長時所形成的免疫特權區,使的免疫細胞無法浸潤腫瘤中,進而辨識及毒殺腫瘤細胞,所以利用藥性溫和的中草藥來提昇宿主之免疫力,亦是本計畫所期待努力的課題。利用小鼠肺癌模式,分析給予中草藥治療後,對於生物體其細胞激素(cytokine)、趨化素(chemokine)分泌及調節型T細胞(regulatory T cell)活化情形作深入的探討。並且評估利用生物活體冷光儀(in vivo bioluminescence imaging system)來即時監控中草藥對於肺癌腫瘤生長和遠端轉移的現象。並綜合研究成果發展雞尾酒式治療策略,合併傳統化學治療,加強肺癌治療效果,減少副作用及抗藥性的產生。
關鍵字:肺癌;中草藥;基因體學

Establishing platforms for screening Chinese herbs as lung cancer drugs using genomic approaches (3-1)

jau - liang wu
National Cheng Kung University Hospital
Lung cancer is the most important cause of cancer death in the world and in Taiwan. In Taiwan adenocarcinoma is the most common type of lung cancer that tends to localize in the periphery of the lung and invade through the pleura to cause pleural effusion at an early stage. Since potentially curative treatments are unavailable, the prognosis of those lung cancer patients with malignant pleural effusion is extremely poor. The pleural involvement of lung cancer is, therefore, a grave problem in Taiwan and studies to dissolve this problem are of urgent importance. Chinese herb extracts have been widely used for the treatment of a variety of chronic disease and cancer. Unfortunately, most of these treatments have been suffered from the lack of stringent clinical trials and evidence-based scientific evaluation. In this grant proposal, we aim to develop platforms for screening Chinese herbs which are capable of down-regulating the transcriptional activities of the promoters that drives the expression of molecules related to cancer formation and/or progression. Furthermore, we will test the tumoricidal and anti-metastatic activities of the candidate Chinese herbs.
關鍵字:lung cancer;Chinese herbs;genomic approaches