林榮耀 國立臺灣師範大學

肝細胞癌（HCC）在台灣地區是最常見且致死率排名第二的癌症，而致癌基因，肝型脂肪酸結合蛋白（L-FABP）在肝癌中具高度表現量。我們先前的研究成果指出 L-FABP 可以藉由促進VEGF-A及MMP-2表現，增加 HEK293 細胞以及immortalized human hepatocyte（Hus）轉移與侵襲的能力，而在小鼠異種皮移植實驗中也有顯著的成果。由於中草藥被視為具有預防與治療腫瘤的能力，因此，在此計畫中，我們將利用已建立之穩定表現L-FABP細胞株作為篩選這些化合物與中草藥的平台，並研究其細胞之增生、遷移、侵襲與血管新生的能力。利用免疫缺陷小鼠模式可進一步確定這些化合物是否具有發展為肝細胞癌化療藥物之潛力。目標一：我們將於四十種中草藥中篩選並找出低細胞毒性且能抑制L-FABP穩定表現細胞株增生、遷移及侵襲之目標。目標二：我們將探討目標中草藥抑制L-FABP穩定表現細胞株中VEGF-A及MMP-2的表現量之機制。目標三：我們將研究中草藥對L-FABP影響的相關訊息傳遞路徑之作用。目標四：我們將研究中藥是否有抗肝癌之成份或對現有抗癌化療藥物治療之輔助療法。目標五：利用免疫缺陷小鼠模式進一步確定這些化合物是否具有發展為肝細胞癌化療藥物之潛力。此計畫將利用致癌基因：L-FABP穩定表現之細胞株去篩選及評估中草藥應用於過度表現L-FABP的肝細胞癌病人治療之可能性。我們也將找出目標中草藥水萃物中的活性成分以作為發展新穎抗癌藥物之先導化合物。

關鍵字：中草藥、肝癌、肝型脂肪酸結合蛋白、遷移、侵襲

Chinese herbal medicine targeting liver type fatty acid binding

Jung-Yaw Lin National Taiwan Normal University

cellular carcinoma (HCC) is one of the most human common cancers and the second cause of cancer-related deaths in Taiwan. Oncogenic gene, liver type-fatty acid binding protein (L-FABP), was shown to be highly expressed in liver cancer. Recently, our preliminary results showed that L-FABP increased the migration and invasion level of HEK293 and immortalized human hepatocyte (Hus) cells by up-regulating the expression level of VEGF-A and MMP-2. L-FABP also promoted tumor growth and metastasis significantly by xenograft analysis. In this project, we will use established stable clones of L-FABP as a platform for screening CHMs, and chemotherapeutic anticancer drugs, and to study the inhibitory effects on cell proliferation, migration, invasion and angiogenesis. Immunodeficient mice model can further determine whether these CHMs have potential for developing clinical chemotherapeutic drugs for HCC therapy. Aim 1: We will screen 40 kinds of CHMs and identify targets with high ratio of cytotoxicity/ inhibitory activity of migration and invasion on L-FABP stable clones. Aim 2: We will study the mechanism of CHMs inhibiting the VEGF-A and MMP-2 expression on L-FABP stable clones. Aim 3: We will discuss the effects of CHMs on L-FABP related signaling pathways. Aim 4: We will study anti-HCC compounds in CHMs. Aim5: We will perform in vivo NOD/SCID mice model experiment to examine whether these CHMs are the potential chemotherapeutic compounds for the treatment of HCC. This project will take advantage of the oncogene: L-FABP stability expressed cell lines to screen and evaluate the possibility of CHMs applying to HCC patients with overexpression of L-FABP. We will also identify the active ingredients of CHMs in the water extracts as lead compounds for developing novel anti-cancer drugs.