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研究生:林育昰
研究生(外文):LIN, YU-SHIH
論文名稱:牛樟芝萃取物對賀爾蒙療法無效攝護腺癌之作用及機轉研究
論文名稱(外文):Studies on the Effect and Mechanisms of Extract from Antrodia Cinnamomea in Hormone Refractory Prostate Cancer
指導教授:張德卿吳清源吳清源引用關係
指導教授(外文):CHANG, DE-CHINGWU, CHING-YUAN
口試委員:曾志正劉怡文江明格沈正煌
口試委員(外文):TZEN, JTCLIU, YI-WENCHIANG, MING-KOSHEN, CHENG-HUANG
口試日期:2020-07-17
學位類別:博士
校院名稱:國立中正大學
系所名稱:生命科學系分子生物研究所
學門:生命科學學門
學類:生物科技學類
論文種類:學術論文
論文出版年:2020
畢業學年度:108
語文別:中文
論文頁數:50
中文關鍵詞:牛樟芝攝護腺癌DU145docetaxel
外文關鍵詞:Antrodia cinnamomeaprostate cancerDU145docetaxel
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攝護腺癌為男性第二常見癌症,2018年全世界有130萬新病例被診斷出。過去研究發現,牛樟芝萃取物能抑制攝護腺癌細胞增生。然而;牛樟芝對不同非雄性素依賴型攝護腺癌細胞的作用與潛在機轉目前仍未清楚。
本研究目的在探討牛樟芝乙醇萃取物(EEAC),於攝護腺癌細胞DU145中的抗癌活性。實驗以XTT,傷口癒合和與細胞侵襲試驗,分別探討EEAC對DU145細胞增生率、遷移與侵犯能力之影響。另利用流式細胞儀、西方點墨法與即時聚合酶連鎖反應分析,探討EEAC抗癌活性機轉,並進一步評估EEAC合併docetaxel (DTX)對DU145細胞產生的作用。
結果顯示,EEAC可有效抑制攝護腺癌DU145細胞之增生、遷移與侵犯能力,並且呈現劑量和時間依存性活性。而EEAC抑制DU145細胞中skp2 mRNA表達並降低蛋白生合成,進而降低CDK2表現造成細胞週期停滯於G0/G1 phase。此外,EEAC可以透過下調粒線體膜電位與增加Cl-PARP表達誘導細胞凋亡反應。另一方面,EEAC顯著提高DTX誘導Cl-PARP表達,這表示EEAC合併DTX可增強DTX誘導細胞凋亡作用。

Prostate cancer (PC) is the second most common cancer in men. In 2018, 1.3 million new cases of PC were diagnosed worldwide. Previous studies have reported that the ethanol extract of Antrodia cinnamomea (AC) can inhibit the growth of PC cell lines. Nevertheless, we don’t know the effects of extract from AC on the different androgen-independent PC cells and the underlying mechanism remain unclear.
This study investigated the anticancer effects of ethanol extracts from AC (EEAC) in DU145 cells by using XTT, wound healing, and cell invasion assay. We explored the underlying mechanism with flow cytometry, Western blot, and q-PCR assay. Furthermore, XTT and Western blot were used to evaluate the synergistic effects of EEAC combined with docetaxel (DTX).
Our study showed that the ethanol extracts of EEAC could inhibit the proliferation, migration, and invasion capacity in a dose- and time-dependent manner in DU145 cells. Moreover, EEAC inhibited skp2 expression at the mRNA and protein levels to suppress the expression of CDK2, which resulted in cell cycle arrest at the G0/G1 phase and promoted apoptosis through MMP downregulation and increased Cl-PARP expression. The combination of EEAC and DTX increased cytotoxicity. Moreover, Western blot data showed that the combined treatment of EEAC and DTX significantly increased Cl-PARP expression compared with single-agent treatment. This suggests that EEAC enhances DTX-induced apoptosis effects in DU145 cells.

目 錄 I
略 字 表 Ⅲ
圖 目 錄 V
中文摘要 Ⅵ
英文摘要 Ⅶ
第一章 背景介紹
一、攝護腺癌 1
二、牛樟芝 4
三、研究動機 6
第二章 材料方法
一、研究材料 7
二、實驗方法 8
三、統計方法 12
第三章 實驗結果
一、牛樟芝乙醇萃取物對攝護腺癌細胞增生率之影響 13
二、牛樟芝乙醇萃取物對DU145抑制細胞增生之機轉 15
三、合併牛樟芝乙醇萃取物與docetaxel,對DU145細胞之影響 18
第五章 討 論 20
第六章 結 論 23
參考文獻 24
實驗結果圖 32

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