肝癌為世界第二大癌症；癌症死亡率第三的癌症，許多藥物被用來治療肝癌如doxorubicin或sorafenib等藥物。本研究中我們的目的主要為探討牛樟芝萃取液(EAC)對於Sorafenib誘導肝癌細胞死亡機制的影響。當合併EAC與sorafenib處理時顯著抑制Huh-7和HepG2的生長，而在Western blot分析出多種訊號顯示合併藥物處理可以調節MAPK和NF-B的路徑達到抗腫瘤的功效，也會誘導細胞週期蛋白表達的改變。以傷口癒合試驗探討合併藥物治療對Huh-7細胞遷移機制的影響；以real time-PCR檢測合併治療對Huh-7細胞的轉移相關蛋白的表現。並且以動物試驗探討合併藥物治療對於肝腫瘤生長的影響。發現合併治療有抑制MAPK家族及細胞週期相關蛋白的表達、抑制增殖能力和降低遷移相關蛋白的表現量。結果顯示EAC能增強Sorafenib誘導細胞死亡能力、增加肝癌細胞對sorafenib的敏感度及抑制肝癌細胞的遷移能力，依此結果運用在肝癌治療中建議EAC可以降低Sorafenib藥量，對於因過量使用Sorafenub患者而產生的副作用的患者，將有相當大的助益，對於未來將進一步探討Sorafenib在EAC的輔助下其更多的機制。 Hepatocellular carcinoma (HCC) is the second-leading cause of cancerworldwide and the third-leading cause of cancer death, and varied drugs wereused to treatment in HCC such as doxorubicin or sorafenib. In the present study, we want to investigate the effects Antrodia Cinnamomea extracts (EAC) on the anticancer activity of sorafenib treatment in HCC cells. First of all, combination treatment resulted in significant growth inhibition in HepG2 and Huh-7 cells.Western blot analysis of various signaling markers revealed the ability ofsorafenib with EAC to target pathways mediated by mitogen-activated protein(MAP) kinase and NF-kB, of which the concerted action underlined itsantitumor efficacy. The combination treatment also induced alternation of cyclin proteins expression. Besides, the Wound Healing assay were perform to study the influence of combined drugs treatment on Huh-7 cells migration mechanism.After that, the MMP-2 and MMP-9 Protein expression of combined drugs treatment on Huh-7 was detected by Quantitative PCR. Finally, in animal model assay were performed to study the influence of combined drugs treatment on HCC tumor growth and protein expression. We found that combination IV significantly inhibition of MAPK family and cell cycle protein expression, inhibition of cell proliferation and reduce protein expression of migration. Our results indicate that EAC can enhance sorafenib for the treatment of HCC cells and enhance sensitivity of sorafenib and inhibition of migration in HCC cells.These results suggest that the EAC is very helpful to reduce the amount of sorafenib, and decreased the side effects of sorafenib on patients in further. We will be further investigating sorafenib in the auxiliary EAC its additional mechanisms.
