中草藥抗肝癌轉移之研究

林榮耀
國立臺灣師範大學
中草藥被視為具有預防與治療腫瘤的能力。最近研究證明中草藥藉由促進抗癌藥物的毒殺能力、減少化學療法的毒性及抑制癌細胞之侵犯與轉移而可能作為治療腫瘤療法之一。我們最近篩選十種中草藥的抗癌活性，發現川山椒水萃物具有抗癌活性，能明顯抑制肝癌細胞的移行與侵犯能力；我們也證明川山椒水萃物可抑制肌動蛋白絲形成並減少癌細胞爬行相關基因FAK 之活化。基於這些初步的研究成果，在此計畫中將探討以下目標：
目標一：我們將於實驗動物模式驗證川山椒的抗癌能力。
目標二：我們將探討川山椒對受體型酪胺酸激脢之表現與活化。
目標三：我們將研究川山椒對FAK影響之Rho GTPase的作用。
目標四：我們將研究川山椒對FAK影響的相關訊息傳遞路徑之作用。
目標五：我們將評估川山椒對抗癌化療藥物治療之輔助療法。
目標六：我們將分析川山椒的活性成分。
此計畫將對川山椒水萃物的抗癌分子機制做詳細的研究，並評估其臨床應用於晚期肝癌病人治療之可能性。我們也將鑑定川山椒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、癌細胞移行、轉移、川山椒
 
Investigating anti-metastatic mechanism of Chinese herbal medicine to hepatocellular carcinoma cells

Jung-Yaw Lin
National Taiwan Normal University
Chinese herbal medicines (CHMs) have been considered as an important source for cancer prevention worldwide. Recent reports demonstrated that CHMs have the potential to be one kind of cancer chemotherapies by enhancing the efficacy of anticancer drugs, reducing chemotherapy toxicity and inhibiting invasion and metastasis of cancer cells. Recently, we examined anticancer activities of ten kinds of CHMs, and found that the aqueous extracts of Zanthoxylum bungeanum Maxim (ZB-A) exhibited higher IC50 growth/IC50 migration ratio than other CHMs to hepatocellular carcinoma (HCC) cells. The results also demonstrated that the treatment of ZB-A inhibited the formation of actin filament and the activation of FAK in HCC cells. Based on our preliminary results, the following specific aims will be investigated in this project.
Aim 1: To investigate in vivo inhibitory effects of ZB-A on HCC cells by mice xenograft model
Aim 2: To examine inhibitory effects of ZB-A on the expression and activity of receptor tyrosine kinases in HCC cells;
Aim 3: To investigate the influence of ZB-A on the activation of Rho GTPases in HCC cells
Aim 4: To explore the signaling pathways suppressed by the treatment of ZB-A in HCC cells
Aim 5: To explore synergic effects of ZB-A with traditional cancer therapies and target therapies to HCC cells
Aim 6: To identify the active component (s) in ZB-A by liquid-liquid partition and high-pressure liquid chromatogram (HPLC)
In this project, the anti-cancer mechanism for the inhibition of ZB-A on HCC cells will be elucidated. We will further evaluate the therapeutic potential of ZB-A for the treatment of HCC patients with late stage and combination with chemotheraphies and target therapies. The active components in ZB-A will be identified to be used as lead compounds for developing novel anti-cancer drugs.
關鍵字：Chinese herbal medicine, Hepatocellular carcinoma, cancer cell migration, tumor metastasis, Zanthoxylum bungeanum Maxim