樟芝，學名Antrodia camphorata，別名有樟菇、樟菰、樟內菇、牛樟菇、紅樟、樟窟內菰等，為台灣特有之真菌，屬台灣特有種，先前文獻指出高濃度樟芝會對肝癌細胞造成毒殺效果，而且許多的研究報告都是給予樟芝後造成癌細胞凋亡，本實驗主要是探討樟芝對抗腫瘤細胞之輔助化療藥物角色。首先藉由細胞毒殺性分析篩選抗癌藥物，分別將抗癌藥物分成不同的族群（包括敏感、中度敏感、不敏感型），再合併使用對肝癌細胞無毒殺效果的樟芝濃度，觀察樟芝是否會改善肝癌細胞對抗癌藥物的敏感度，並探討其分子機制。低濃度樟芝可協同抗癌藥物抑制肝癌細胞存活率，是經由降低多藥抗藥性（Multidrug resistance；MDR）的產生，或是與抗癌藥物合併後加強其毒殺細胞作用，接著利用西方墨點法分析MDR路徑相關的蛋白質（例如：COX-2, Akt, PARP-1）。應用流式細胞儀技術檢測樟芝與抗癌藥物合併後是作用於細胞週期何處而引起細胞凋亡抑制肝癌細胞生長。
經由上述實驗發現肝癌細胞合併低濃度樟芝與不同作用機制的抗癌藥物後，調節肝癌細胞中多藥抗藥性（Multidrug resistance；MDR）相關蛋白的表現而使肝癌細胞抗藥性降低，造成藥物更易進入肝癌細胞中，因而增加了藥物累積量，同時也會降低P-gp作用以減少藥物排出量，最終使細胞走向凋亡一途。透過降低MDR表現同時促進抗癌藥物對細胞凋亡毒殺作用之結果推斷樟芝與抗癌藥物合併時是扮演一輔助性角色。

Antrodia camphorata (AC), a unique fungal species, used as a folk medicine in Taiwan. Hepatocellular carcinoma (HCC) is one of the most prevalent cancers, often respond with limited efficacy to currently available chemotherapeutics with multidrug resistance (MDR) expression. The present study were to establish an evaluation system on MDR, compare the adjuvant anti-cancer effects from ACs mycelia on the human hepatoma cell lines (HepG2, C3A and PLC/PRF/5),
which cause resistance to most chemotherapies.
The results indicated that cisplatin and paclitaxel can cause drug resistance and MDR-1 expression were positive on high dose (10M), while another (Mytomyocin) were more sensitivity and the MDR-1 expression were negative. Meanwhile, we found that diverse ACs on high dose also caused the cytotoxicity by MTT assay as well as the inhibition of MDR-1 expression by western blotting (100M) such as some chemotherapies induction above. Interestingly, the regiment of ACs treatment (<10M) combined with chemotherapies to HCC can potentate the anti-cancer activities and decreased MDR-1 expression, but ACs (>10M) treatment alone also induced the cytoxicity to normal liver cell (BNL).
Our data indicated that treated AC combined with chemotherapies can decrease MDR-1 expression through inhibition COX-2, P-Akt, and increase the PAPR-1 expression to HCC by western blotting. So, we believed that AC may play a important role of adjuvant chemotherapies to regulate MDR for HCC. Continuously, the cell cycle pase and apoptosis percentage (FACS) testing in vitro and in vivo model (ICR nude mice implanted liver tumor cells) to the effect of ACs with chemotherapies will be done.

中文摘要……………………………………………………………………………Ⅰ
Abstract…………………………………………………………………………Ⅲ
目次…………………………………………………………………………………Ⅴ
表目錄………………………………………………………………………………Ⅵ
圖目錄………………………………………………………………………………Ⅶ
縮寫對照表…………………………………………………………………………

第一章 文獻回顧……………………………………………………………………1
1.1樟芝簡介……………………………………………………………………1
1.1.1樟芝成分分析………………………………………………………4
1.1.2樟芝生理活性成分…………………………………………………5
1.1.3樟芝安全性相關試驗………………………………………………7
1.1.4樟芝功能性研究……………………………………………………9
1.2肝臟簡介……………………………………………………………………23
1.2.1肝癌簡介…………………………………………………………24
1.2.2肝癌病因……………………………………………………………28
1.2.3肝癌治療……………………………………………………………29
1.3多藥抗藥性…………………………………………………………………35
1.4腫瘤細胞多藥耐藥機制……………………………………………………36
1.5與多藥抗藥相關蛋白………………………………………………………48

第二章 研究動機與目的…………………………………………………………54

第三章 研究材料與方法…………………………………………………………56

第四章 結果與討論………………………………………………………………80

第五章 結論……………………………………………………………………102

第六章 結果圖表………………………………………………………………106

第七章 參考文獻………………………………………………………………157

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