臺灣博碩士論文加值系統

靈芝是一種中國流傳已久的藥用真菌，被視為上等的中藥材，近年來，有許多研究顯示靈芝具有免疫調節、抗氧化及抗癌等功效。松杉靈芝為台灣常見的靈芝品種，許多文獻指出松杉靈芝的萃取物有廣泛抑制人類癌細胞生長的效果，包括乳癌、卵巢癌、大腸癌、皮膚癌、肝癌和肺腺癌等，但松杉靈芝對子宮內膜癌的抗癌功效尚未被證實。本研究探討松杉靈芝的乙醇萃取物 (GTE) 對子宮內膜癌的抗癌效果及相關分子機制。經由 MTT assay 及 Trypan blue assay 的實驗結果顯示， GTE 會抑制子宮內膜癌細胞 HEC-1-A, KLE 及 AN3 CA 的生長。實驗結果也證明 GTE 會經由影響細胞週期的調控蛋白，如Cyclins 及 p27 等，進而造成子宮內膜癌細胞的細胞週期停滯而抑制其生長。同時，進一步探討 GTE 誘發子宮內膜癌細胞的細胞凋亡作用機制及其影響的訊息傳遞路徑。最後，本論文研究結果顯示， GTE 在子宮內膜癌的臨床治療上，可能作為一個有用的輔助治療藥劑。

Ganoderma, also known as Lingzhi, is a traditional Chinese medicine that has been used for medicinal purposes in Asian countries for centuries. It has a wide variety of biological properties including immunomodulatory, antioxidation and anticancer activities. Ganoderma tsugae (GT), one of the most common species of Ganoderma cultivated in Taiwan, has been reported that GT extract (GTE) has growth-inhibitory effects on a variety of human cancer cells, including breast cancer, ovarian cancer, colorectal cancer, epidermoid carcinoma, hepatoma, and lung adenocarcinoma. However, the anticancer effect of GT on endometrial cancer (EC) is still unclear. In this study, we investigate the anticancer effects of GTE and related molecular mechanisms in endometrial cancer cells. The results of MTT assay and trypan blue assay indicate that GTE inhibits the proliferation of EC cell lines HEC-1-A, KLE, and AN3 CA.Our data also indicate that GTE induces cell cycle arrest by interfering with the expression of cell cycle regulators such as cyclins and p27. We further study how GTE induces EC cell lines apoptosis and related pathway. In the final, this study suggests that GTE may be a useful adjuvant therapeutic agent in the treatment of EC.

目錄 i
中文摘要 v
Abstract vi
縮寫表 vii
致謝 ix
第一章　緒論 1
　第一節、子宮內膜癌 (Endometrial Cancer ) 1
　第二節、靈芝 (Ganoderma, Reishi, Lingzhi) 5
　第三節、細胞週期 (Cell Cycle) 12
　第四節、細胞凋亡 (Cell Apoptosis) 15
　第五節、調控細胞生長及存活之 PI3K/Akt 訊息傳遞路徑 21
第二章　研究動機與目的 23
第三章　結果與討論 24
　第一節、GTE 對HEC-1-A, KLE 及 AN3 CA子宮內膜癌細胞株生長之影響 24
　第二節、GTE 使 HEC-1-A, KLE及AN3 CA 子宮內膜癌細胞株的細胞週期停滯 30
　第三節、GTE 藉由調節 HEC-1-A, KLE及AN3 CA 子宮內膜癌細胞株的細胞週
　　　　　期蛋白使細胞週期停滯 33
　第四節、GTE 藉由活化及裂解 Caspase 3 與 PARP蛋白而誘發HEC-1-A, KLE
　　　　　及AN3 CA 子宮內膜癌細胞的細胞凋亡 37
　第五節、GTE 透過活化粒線體路徑進而誘發HEC-1-A 及 KLE 子宮內膜癌細胞
　　　　　的細胞凋亡 41
　第六節、GTE 可能透過調控 PI3K/Akt 訊息路徑進而抑制HEC-1-A 及 KLE 子
　　　　　宮內膜癌細胞的生長 43
　第七節、討論 45
第四章　結論 50
第五章　材料與方法 51
　第一節、實驗材料 51
　第二節、實驗方法 55
第六章　參考文獻 59
第七章　表 67
第八章　附錄 68

表一、本論文所使用之人類子宮內膜癌細胞株 67
表二、本論文所使用之一級抗體 67
表三、本論文所使用之二級抗體 67

圖A、民國102年台灣國人十大死因死亡率 1
圖B、西元2012年美國男性及女性十大癌症死亡率 2
圖C、西元1990-2012年台灣女性子宮體癌死亡率 3
圖D、民國102年台灣男性及女性十大癌症死亡率 3
圖E、哺乳類動物細胞之細胞週期與相關調控蛋白 15
圖F、細胞凋亡之死亡受體路徑 19
圖G、粒線體膜電位調控機制 20
圖H、細胞凋亡之粒線體路徑 20
圖I、細胞凋亡之內質網壓力路徑 21
圖J、PI3K/Akt 調控路徑及下游相關調控蛋白 22
圖1、以MTT assay檢測 GTE 對子宮內膜癌細胞株的生長抑制作用及半數抑制濃
度 (IC50) 27
圖2、以Trypan blue assay檢測 GTE 對子宮內膜癌細胞株的細胞毒殺作用 28
圖3、GTE對子宮內膜癌細胞 HEC-1-A, KLE 及AN3 CA生長形態之影響 29
圖4、GTE 干擾子宮內膜癌細胞株之細胞週期分布 32
圖5(a)、GTE 影響 HEC-1-A 子宮內膜癌細胞中細胞週期調控蛋白的表現 34
圖5(b)、GTE 影響 KLE 子宮內膜癌細胞中細胞週期調控蛋白的表現 35
圖5(c)、GTE 影響 AN3 CA 子宮內膜癌細胞中細胞週期調控蛋白的表現 36
圖6、GTE 誘發 HEC-1-A, KLE 及 AN3 CA 子宮內膜癌細胞的染色質集結現象 38
圖7(a) & 7(b)、GTE 促進 HEC-1-A 及 KLE 細胞中與細胞凋亡相關的 PARP 與 Caspase-3 蛋白的裂解及活化 39
圖7(c)、GTE 促進 AN3 CA 細胞中與細胞凋亡相關的 PARP 與 Caspase-3 蛋白的裂解及活化 40
圖8、GTE 透過活化粒線體路徑誘發 HEC-1-A 及 KLE 子宮內膜癌細胞的細胞凋亡 42
圖9、GTE 抑制 HEC-1-A 及 KLE 子宮內膜癌細胞中的 PI3K/Akt 訊息路徑 44

附錄一、《神農本草經》原文及對應現代症例 68
附錄二、台灣八大種類靈芝簡介 69
附錄三、實驗架構圖 70
附錄四、GTE 調控子宮內膜癌細胞生長之可能分子機制 71
附錄五、松杉靈芝 (原產品名天生靈芝) 72
附錄六、細胞株培養方法 73
附錄七、松杉靈芝乙醇萃取物 (GTE) 之製備 75
附錄八、西方墨點法使用之試劑及緩衝液 76

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