6-shogaol藉由內質網壓力與氧化壓力誘發Hep - G2細胞凋亡

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標題:	6-shogaol藉由內質網壓力與氧化壓力誘發Hep - G2細胞凋亡 6-shogaol Induces Apoptosis in Hep-G2 Cells through ER stress and Oxidative stress
作者:	黃宏彰
貢獻者:	嘉南藥理科技大學：生物科技系暨研究所洪瑞祥
關鍵字:	細胞凋亡內質網壓力 NAC 氧化壓力肝癌薑 6-shogaol apoptosis ER stress NAC ROS Hep-G2 liver cancer 6-shogaol
日期:	2011
上傳時間:	2011-10-25 15:30:06 (UTC+8)
摘要:	肝癌，長久以來一直是國內癌症死亡率的第一或第二名。近年來的研究顯示，B型肝炎、C型肝炎、肝硬化、酗酒、黃麴毒素等等，都是造成肝癌的原因。根據統計，在台灣的肝癌患者約有百分之八十都是B型肝炎所導致。目前治療肝癌的化學治療藥物有許多，然而因為肝癌的復發率很高，化學治療藥物用量會逐漸上升導致產生抗藥性而失效，所以在肝癌的化學治療藥物值得更進一步的去探討及開發。先前研究發現，一種從薑中萃取出來的化合物6-shogaol，在肝癌細胞中可以透過大量的消耗GSH，造成細胞內ROS含量的累積，進而誘發了細胞的凋亡。本實驗中藉由添加抑制劑NAC抑制ROS後發現，確實能有效的保護細胞因6-shogaol產生的ROS誘發的細胞凋死亡現象，但仍有一部分的細胞還是會死亡，顯示6-shogaol仍會經由其他的機制造成肝癌細胞的死亡。初步結果顯示肝癌細胞經過不同濃度之薑萃取的化合物6-shogaol作用後，肝癌細胞存活率隨6-shogaol濃度增加而遞減。進一步的，當藉由流式細胞儀分析結果顯示，6-shogaol作用下肝癌細胞內在1-3小時會產生大量的ROS，而隨6-shogaol濃度的增加可明顯的改變肝癌細胞的細胞週期，結果顯示6-shogaol 可誘導肝癌細胞的sub-G1和細胞凋亡族群比例也隨之提高。另一方面的結果顯示，6-shogaol會明顯的誘導肝腫瘤細胞株產生內質網壓力，然而當加入ROS抑制劑NAC後，內質網壓力仍然存在。綜合以上實驗結果顯示，薑之萃取化合物6-shogaol會藉由產生大量的ROS和誘發內質網壓力來誘導細胞的死亡，而ROS的產生及內質網壓力為兩個獨立的訊息傳遞路徑，最後期待薑之萃取化合物6-shogaol的抗癌機制能對在治療肝癌上有所幫助。 For long, the liver cancer always is in the first or the second place in the death rate in Taiwan. The studies in the few years shows, HBV, HCV, liver cirrhosis, drink excessively, and aflatoxin …etc.; the reason that above all causes liver cancer. According to the statistics, the patients of the liver cancer of the eighty per cent in Taiwan are all caused by HBV. At present, there are a lot of the chemistry treatment drugs for liver cancer treatment. However, because the rate of the recurrence is very high, the amount used of the chemistry treatment drugs will be higher and produce the drug resistance. Therefore, the drug chemistry treatment in the liver cancer must be more explored and developed. Formerly, the studies find, from the 6-shogaol compound, a kind of the ginger; it can cause the amount adding of the ROS in the cell with consuming GSH massive in the liver cancer cell, and causes the apoptosis. In the experimentation, by increasing the inhibitor of the NAC into the ROS, find that it could protect the cell effectively because the ROS from the 6-shogaol causes the apoptosis. But still, the part of the cell will died, and show the 6-shogaol still causes the death of the liver cancer cell from others. In the first result, the cell of the liver cancer, after extracts the 6-shogaol from the different density of the ginger; the survival rate of the liver cancer cell, can decrease because the consistency of the 6-shogaol increases. Further, from the data of the flow cytometry analysing, the 6-shogaol will produce the large ROS in the cell of the liver cancer, during the first to the third hour, and up to the consistency of the 6-shogaol increases, the cell cycle of the liver cancer cell will be changed; On the other hand, the result, tells that the 6-shogaol will induce obviously the cell strain of the live tumor to produce the ER stress; still is alive the ER stress after add the ROS into the NAC inhibitor. Integrate above all the experiments and shows, the 6-shogaol compound from the ginger will induce the cell to die from producing the large ROS and the ER stress, and both of the ROS and the ER stress will become the two different alone ways for passing messages. Finally, look forward the Anti-cancer mechanisms of the 6-shogaol abstract compound from the ginger could be helpful for liver cancer treatment.
關聯:	校內外均一年後公開，學年度：99，70頁
顯示於類別:	[生物科技系(所)] 博碩士論文

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