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研究生:陳稚唯
研究生(外文):Chih-Wei Chen
論文名稱:探討一氧化氮減少水飛薊素抑制人類肝癌細胞株HepG2生長之機制探討
論文名稱(外文):Study of the Mechanism of Nitric Oxide Reducing Silymarin-induced Growth Inhibition in HepG2 Human Hepatoma Cells
指導教授:戚謹文李新城李新城引用關係
指導教授(外文):Chin-Wen ChiHsin-Chen Lee
學位類別:碩士
校院名稱:國立陽明大學
系所名稱:藥理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:中文
論文頁數:88
中文關鍵詞:ㄧ氧化氮水飛薊素人類肝癌細胞
外文關鍵詞:nitric oxidesilymarinhuman hepatoma cells
相關次數:
  • 被引用被引用:1
  • 點閱點閱:226
  • 評分評分:
  • 下載下載:54
  • 收藏至我的研究室書目清單書目收藏:0
肝癌是致死率很高的癌症,但目前治療方法有限,就算用手術治療,病人的復發率仍然很高,因此發展新的抗肝癌藥物已益趨重要。而近年來有許多研究報告指出水飛薊有抗發炎,清除自由基和減緩肝硬化的效果,也有研究指出silymarin的活性成分silibinin會對人類肝癌細胞造成生長抑制及細胞週期抑制以及減少肝癌細胞HepG2的一氧化氮含量,而有研究指出細胞內的一氧化氮對腫瘤細胞有保護作用。因此本論文首先以水飛薊的萃取物silymarin來處理人類的肝癌細胞株,觀察silymarin對人類的肝癌細胞的生長抑制情形。由MTT的結果發現細胞處理silymarin和silibinin後,可以明顯抑制細胞生長。HepG2細胞處理silymarin 72小時後發現silymarin使細胞型態改變,細胞週期G2/M、subG1期比例增加。而合併處理一氧化氮供給劑sodium nitroprusside (SNP) 0.1 mM後發現,一氧化氮供給劑能夠減少silymarin造成的HepG2細胞生長抑制情形,本實驗進ㄧ步探討silymarin抑制HepG2細胞生長之可能機轉,由西方墨點法實驗結果發現silymarin可以透過調控PI3K/Akt、MAPK等訊息傳導路徑相關蛋白來抑制腫瘤細胞生長,而一氧化氮能夠反轉silymarin的抑制效果,另ㄧ方面,利用一氧化氮清除劑PTIO預處理後發現,PTIO能減少SNP造成的細胞內一氧化氮含量上升,並且有效減少SNP的細胞作用,由這些結果推測SNP減少silymarin對於肝癌細胞生長抑制作用是透過一氧化氮的調節。
Hepatocellular carcinoma (HCC) is one of the most common cancers around the world. Although there are many studies on HCC, effective treatments for HCC are limited. Silymarin is a herbal drug used for the prevention and treatment of liver disease. Previous studies found that silibinin, the major component of silymarin, showed anti-HCC effects and decreased nitric oxide (NO) production in HepG2 cells. Recently, we have demonstrated cytoprotective functions of NO in hepatoma cells. Firstly, the growth inhibitory effects of silymarin and silibinin on human hepatoma cells were compared. The results showed that silymarin-induced growth inhibition of HepG2 cells was dose- and time-dependent, and silibinin treatment resulted in similar response in HepG2 cells. Furthermore, high dose (100, 200 μg/ml) silymarin treatment resulted in round up and fragmented cell morphology in HepG2 cells. Flowcytometry was used to analyze the cell cycle, and the results showed that silymarin treatment slightly increased the percentage of G2/M phase and apoptotic cells at 72 hr. This study further investigated the cytoprotective effect of NO in silymarin-induced growth inhibition of HepG2 cells. Treatment of HepG2 cells with sodium nitroprusside (SNP), a NO donor, increased the NO level dose dependently. Treatment of HepG2 cells with 0.1 mM to 0.5 mM of SNP significantly inhibited the high dose (100~200 μg/ml) silymarin-induced cell growth inhibition. Moreover, it was found that the NO scavenger, PTIO, blocked the cytoprotective effect of SNP in HepG2 cells and this correlated with a decrease of the SNP-induced intracellular NO level. Western blot analysis revealed the mechanism of silymarin-induced growth inhibition, invoved PI3K/ Akt, MAPK and apoptotic pathway. SNP treatment increased the activity and levels of Akt, ERK and IKK�� protein. These results suggested that the effect of NO on modulation of silymarin-induced growth inhibition effect on HepG2 cells may through PI3K/Akt or MAPK pathways. These results together suggest that nitric oxide may partially reverse the inhibtiory effect of silymarin on hepatoma cells.
目錄
謝誌---------------------------i
中文摘要-----------------------1
英文摘要-----------------------2
縮寫表-------------------------4
壹、緒論-----------------------5
貳、實驗目的------------------30
參、實驗項目------------------31
肆、實驗儀器與藥品------------33
伍、實驗方法及進行步驟--------36
陸、實驗結果------------------42
柒、討論----------------------49
捌、結論----------------------54
玖、參考文獻------------------55
拾、圖表----------------------65
拾壹、附錄--------------------87
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