臺灣博碩士論文加值系統

自1984年起，癌症便一直是台灣地區人民死因之首位，而其中，肝癌更是一直獨佔鰲頭，廿年來，醫學科技雖有長足的進步，但對肝癌的治療卻始終停滯不前，因而從傳統中藥當中尋找有效藥物便成了另一個希望。
冬蟲夏草在傳統醫學上，原以補益功能為主。更是許多大陸醫家用於治療癌症患者的補益藥物，他們認為冬蟲夏草具有扶正袪邪之功，而能用於癌症治療之上。在冬蟲夏草的眾多成份中，蟲草素是其中具有抗癌作用的主要成份之一，我們將進行研究蟲草素對肝癌細胞的影響，以及未來用於治療肝癌的可能性。
由於B型肝炎病毒是造成台灣地區人民形成肝癌的主要原因，因而我們設計使用具有B型肝炎病毒DNA序列的中國男性肝癌細株HA22T/VGH為實驗的對象，同時加入不同濃度的蟲草素，以觀察是否會造成HA22T/VGH細胞株的死亡及可能之死亡途徑。
研究結果顯示：隨著時間及劑量之增加，蟲草素對HA22T/VGH細胞株的生長抑制亦隨之增加，最高可達83%。而造成HA22T/VGH細胞株死亡的途徑則包括細胞分裂風暴及細胞凋亡。在加藥處理後的HA22T/VGH細胞株可以見到近40%具有細胞分裂風暴之形態學特徵，同時亦使G2/M phase細胞比例從10.6%上升至16.3%；而細胞凋亡的比例則將近有13%，其中啟動之路徑則包含有Caspase路徑及非Caspase路徑。
蟲草素應具有對抗肝癌細胞之作用，同時亦呼應傳統醫學上冬蟲夏草「扶正袪邪」之效，但蟲草素是否可以直接用於治療肝癌病患，則需進一步的研究發展。

Cancer disease was the primarily killer of the people in Taiwan since 1984. Hetaptoma has been monopolizing the head among them. Although medical science and technology make long-term progress though past twenty years, there were no satisfied treatment and result about hepatoma. So the the traditional Chinese medicine becomes another hope of therapy for hepatoma.
Cordyceps sincesis (Berk.) Sacc. is a supplement in China's traditional medical. Lots of Chinese medical physicians used it for cancer patient supplement, just because they thought it got the function to support right and dispel evil, so that it could be helpful for cancer treatment. In the numerous compositions of Cordyceps sincesis (Berk.) Sacc., one of the main compositions for antineoplasm is cordycepin. Therefore we want to study that the cordycepin impacts on liver neoplasm cells and the possibility for treating of hepatoma in the future.
Because the hepatitis virus B is the main reason that cause hepaotma in Taiwan. Therefore we use HA22T/VGH human hamatoma cell line who encode with hepatitis virus B DNA from a male Chinese to investigate the cordycepin target on it with different concentrations and time. In order to observe whether will cause the death of HA22T/VGH cell line and possible death ways, we use equipments of cell counter chamber, microscope, flow cytometer, DNA electrophoresis and western blots ect. to complete it.
The results show that with the increase of the time and dosage of cordycepin, the growth of HA22T/VGH cell line is suppressed and the inhibition rate can reach as high as 83%. The possible pathways of HA22T/VGH cell line death include mitotic catastrophe and apoptosis. The morphology characteristics of mitotic catastrophe was nearly 40% in the HA22T/VGH cells treated with cordycepin, and the percentage of G2/M phase increase from 10.6% to 16.3% was observed. Almost 13% cell will undergo apoptosis, and the pathways of apoptois include caspase-dependent and caspase-independent.
According to the experimental results, We can suppose that the cordycepin get the function to against hepatoma, it also echo the concept of support right and dispel evil of Cordyceps sincesis (Berk.) Sacc. in traditional Chinese medicine. However, could the cordycepin be used for hepatoma therapy, it still need further research to support it.

第一章 肝癌與冬蟲夏草之初探
第一節 研究背景及目的...................................1
第二節 中醫腫瘤學之淺談.................................5
第三節 冬蟲夏草與蟲草素之簡介............................11
第四節 癌細胞死亡形態之初探..............................20

第二章 研究方法與材料
第一節 細胞培養.........................................39
第二節 藥物之處理........................................39
第三節 細胞生長抑制率之測量...............................40
第四節 細胞形態(Morphology)之觀察........................41
第五節 細胞週期(Cell Cycle)之測量........................43
第六節 細胞凋亡比例之量測.................................46
第七節 粒線體膜電位之量測.................................47
第八節 Caspase family活性之量測..........................49
第九節 DNA電泳..........................................50
第十節 西方墨點法(Western Blot)之分析.....................51

第三章 實驗結果
第一節 細胞數量及細胞生長抑制率............................55
第二節 細胞形態(Morphology)之變化.........................57
第三節 細胞週期(Cell Cycle)之變化.........................60
第四節 細胞凋亡比例.......................................62
第五節 粒線體膜電位之變化..................................62
第六節 Caspase family活性之變化...........................63
第七節 DNA電泳結果........................................64
第八節 西方墨點法(Western Blot)之結果......................65

第四章 討論
第一節 蟲草素與HA22T/VGH之生長抑制.........................69
第二節 蟲草素與HA22T/VGH細胞形態之變化......................70
第三節 蟲草素與HA22T/VGH細胞之DNA斷裂......................70
第四節 蟲草素與HA22T/VGH細胞週期之變化......................73
第五節 蟲草素與HA22T/VGH細胞凋亡...........................75
第六節 蟲草素與HA22T/VGH細胞分裂風暴.......................78
第七節 冬蟲夏草與扶正袪邪之相關性...........................79
第八節 總結...............................................81

第五章 結論與建議.........................................82

表一 蟲草素對HA22T/VGH之生長抑制...........................99
表二 蟲草素對Hep3B之生長抑制...............................100
表三 Caspase Inhibitors對蟲草素抑制HA22T/VGH生長之影響......101
表四 細胞分裂風暴比例.......................................102
表五 Sub-G1百分比.........................................103
表六 細胞週期之變化........................................104
表七 進行細胞凋亡之細胞比例..................................105
表八 粒線體膜電位變化率......................................106
表九 Caspase Inhibitors對粒線體膜電位變化率之影響.............107
表十 Caspase family活性變化比值.............................108

圖一 HA22T/VGH肝癌細胞株之生長曲線..........................109
圖二 Liu’s stain染色法....................................110
圖三 Immunofluorescence Stain染色法........................111
圖四 PI Stain染色法........................................112
圖五 PI stain之流式細胞儀圖.................................113
圖六 PI and BrdU stain之流式細胞儀圖........................114
圖七 PI and Phospho-Histone H3 Stain之流式細胞儀圖..........115
圖八 細胞凋亡測試之流式細胞儀圖...............................116
圖九 粒線體膜電位變化之流式細胞儀圖............................117
圖十 Caspase family活性比值柱狀圖............................118
圖十一 DNA電泳圖.............................................119
圖十二 Western blotting of Caspase-3, 8, 9..................120
圖十三 Western blotting of Caspase-2, 7.....................121
圖十四 Western blotting of AIF, EndonucleaseG...............122
圖十五 Western blotting of cytochrome C, Smac and Omi.......123
圖十六 Western blotting of Bcl-2 and Bax....................124
圖十七 Western blotting of p53..............................125

附錄一 中醫腫瘤病因分析表.....................................126
附錄二 中醫腫瘤病機分析.......................................127
附錄三 B型肝炎病毒與肝癌之病因、病機演變........................128
附錄四 細胞死亡之型態.........................................129
附錄五 調控細胞凋亡的Bcl-2 Family.............................130
附錄六 細胞凋亡誘發途徑示意圖..................................131

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