人類癌症基因體以驗證探討抗癌中草藥-子計畫二、中草藥調節生長因子及其接受器基因對抗肝癌機制的探討
吳永昌
高雄醫學大學
肝癌為為國人男性癌症死因第一名，台灣每年約有5000人死於肝癌。手術切除是肝癌唯一根治性的治療；然而大多數病人無法以外科手術切除肝癌，也對現有化學藥物治療的藥效反應及預後均不理想。因此，研發新的抗肝癌藥物乃是醫藥界迫切的目標。中草藥的豐富性及悠久的學理基礎提供現代藥物研究者最好的寶庫。本群體計畫即根據歷代中藥典籍及台灣常用藥用植物中選出60種中草藥單方及複方來進行抗肝癌研究。根據本計畫總主持人林榮耀院士的研究團隊先前研究顯示，利用 cDNA microarry的技術，針對肝癌細胞及正常細胞的比對分析，鑑定出67種基因在肝癌細胞有異常表現，包括致癌基因、抑制癌基因、細胞凋亡基因、生長因子及其接受器基因、血管新生基因、癌細胞轉移、浸潤以及細胞週期基因。在本子計畫中，我們擬針對肝癌相關的生長因子與其接受器基因（如IGF-2, MET, ERBB2），以及致癌基因(如RAS, RAF-1, MYC),以相關之promoter-reporter assay進行上述中草藥的作用篩選，並以RT-qPCR及Western blot等技術來進一步確認它們對上述基因調控的影響。另外我們也會以MTT assay與colony assay測試這些中草藥萃取物對人類肝癌細胞株的抗癌作用。最後，我們也將選取具有潛力的中草藥萃取物進一步進行肝癌腫瘤實驗動物實驗，以「證據基礎」鑑定中草藥之抗癌功能。我們預期本計畫希望本試驗可以為臨床前試驗打下基礎，未來可再規劃臨床試驗進行人體試驗，以驗證其抗腫瘤之確效，提供中草藥之科學化驗證。
關鍵字：中草藥；抗腫瘤；基因體分析
Evidenced-base studies on anticancer of Chinese herbs by genomic medicine-subproject 2: Studies on the anticancer activity of Chinese herbs: regulation of growth factors-related genes
Yang-Chang Wu
Kaohsiung Medical University
Hepatocellular carcinoma (HCC) is one of the most common malignancies in Taiwan and in many other countries. Although surgery is considered the best treatment option, most patients with HCC are not eligible for surgery at the time of primary diagnosis. Unfortunately, HCC is resistant to conventional chemotherapy, and is rarely amenable to radiotherapy, leaves this disease with no effective therapeutic options and a very poor prognosis. Therefore, the development of more effective therapeutic tools and strategies is much needed. The classical Chinese pharmacopoeia describes a large number of herbal formulations that are used for the treatment of liver diseases and may provide a valuable resource for the discovery of novel therapeutics of HCC. In this subproject, we have selected 60 herbs and complex formulations from classical Chinese pharmacopoeia and Taiwanese herb books, and we are planning to test these herb extracts for their effects on 5 human liver cancer cell lines. In a preliminary study, Dr. Lin has identified 67 genes which are abnormally expressed in HCC, including oncogenes, tumor suppressor genes, and genes related to apoptosis, angiogenesis, metastasis, and cell growth.
關鍵字：Chinese herbal medicine；anti-tumor；genome assay
