肝癌是世界五大癌症之一，使得肝癌在癌症所致之死亡率高居不下，是由於診斷及預後困難。手術、酒精栓塞、放射治療、換肝及化學治療是目前治療肝癌的主要治療方式，但最後還是得面臨化學治療。然而肝癌在治療時很容產生抗藥性因而限制了治療的效果。因此，在肝癌治療上開發一種更有效的治療策略是目前迫切需要。先前研究發現，compound 1，在肝癌細胞中發現可以透過大量的消耗 GSH，造成細胞內 ROS 含量的累積，進而誘發了細胞的凋亡。另一方面，sorafenib為已被批准用於原發性腎癌和肝癌的治療藥物，是一種激?抑製劑的標靶藥物，是目前治療肝癌的主要標靶藥物。本實驗主要評估，臨床肝癌標靶用藥 sorafenib 與 compound 1 結合誘導肝癌細胞死亡的治療效果。在合併處理時下利用 MTT 方法分析發現可以明顯誘導 Huh-7 和 HepG2 細胞死亡。進一步利用 annexin V 和 caspase-3 活性分析發現在合併處理後可以明顯增強細胞凋亡，但無增強 caspase-3 的活性。此外，在合併處理下 ROS 抑制劑無法明顯的抑制細胞死亡。這樣結果顯示還有另一條路徑調控在 sorafenib 結合 compound 1 處理後所誘導的細胞死亡。實驗結果發現 Huh-7 在 sorafenib 結合 compound 1 處理後，抑制細胞生長效果比單獨處理更佳，具有加乘效應。然而，合併處理所誘導的細胞死亡的機制進一步的探討。 Hepatocellular carcinoma (HCC) is the ?fth most common malignancy worldwide. High mortality of HCC is due to the difficulty in diagnosis and poor prognosis. Chemotherapy is a traditional choice for inoperable HCC, whereas drug resistant limits the therapeutic effect. Thus, there is an urgent need to develop a potential therapeutic strategy for HCC.Formerly, from the compound 1, it can cause the amount adding of the ROS in the cell with consuming GSH massive in the liver cancer cell, and causes the apoptosis. Sorafenib is a drug approved for the treatment of primary kidney cancer and HCC. Sorafenib is a type of targeted therapy known as a kinase inhibitor. This study was to evaluate the effect of compound 1 on sorafenib-induced hepatocellular carcinoma cell death. Enhanced Huh-7 and HepG2 cells death were observed in combination therapy by using MTT assay. In addition, the data indicated that enhanced cell death by combination therapy was partially involved in apoptosis in HepG2 cells, and it characterized by annexin V assay and caspase-3 activity assay. Furthermore, ROS production do not involve in combination therapy-induced cell death in Huh-7 cells. In the present study, combination of compound 1 with sorafenib promotes growth inhibition of Huh-7 cells and produces an additivity effect. However, the mechanisms of combination therapy-induced cell death need to determine in the future.
