GST isoforms 於正常肝細胞及肝癌細胞中生理功能之探討及其對防抗癌天然物開發之應用

中山醫學大學機構典藏 CSMUIR > 醫學院 > 生化微生物免疫研究所 > 研究計劃 > Item 310902500/3106

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Title:	GST isoforms 於正常肝細胞及肝癌細胞中生理功能之探討及其對防抗癌天然物開發之應用 Study of the Fuctions of GST Isoforms in Normal and Cancerous Liver Cells and the Application in the Developsment of Chemopreventing and Anticancer Agents
Authors:	周芬碧 Chou, Fen-Pi
Contributors:	中山醫學院生物化學研究所
Keywords:	麩胱甘硫轉移;短暫轉殖;肝癌細胞;生理功能 GST isoforms;Transition transfection;Hepatoma cells;Physical function
Date:	2005
Issue Date:	2010-12-07T09:24:05Z (UTC)
Abstract:	Glutathione S-transferases（ GSTs）是一類具多功能的蛋白質，為哺乳動物細胞中一重要的解毒酵素，它可以催化 GSH 與攻擊 DNA 的親電性外來物質結合，並將之代謝排出體外。雖然在正常肝細胞內扮演解毒及保護細胞的角色，可是近年來對於肝癌的研究發現肝臟解毒酵素 GSTs 的異常表現可能與肝癌的形成有密切的關係，若是某些族的 GSTs 發生異常改變，則可能造成癌症或是抗藥性的形成。然而至今對於不同族之 GSTs 的差異表現與不同因素所導致的肝癌或是抗藥性的發生之間的關聯仍然不是很清楚。因此本實驗利用 GST 短暫殖入系統探討 GSTs 對人類肝癌細胞 Hep G2、 Hep 3B 及 Chang liver 細胞生長、型態及其對致癌物反應之影響。結果顯示，將 rGSTYb1 殖入 Chang liver 細胞後，再以 AFB1 處理細胞，細胞的存活率比轉殖入 pEGFP 載體之細胞來的高，且肝細胞毒性指標 GOT 及 GPT 的活性較低，而 GSTAl 及 GSTPi 的活性則沒有顯著差異，表示 rGSTYb1 的表現可保護 Chang liver 細胞並減緩 AFB1 對 Chang liver 細胞的傷害。而將 rGSTYb1 殖入 Hep G2 細胞、人類 GST A2 轉殖入 Chang liver 細胞及 Hep 3B 細胞後，再以 AFB1 處理細胞，卻得到相反的結果；細胞的存活率比轉殖入 pEGFP 載體之細胞低，且肝細胞毒性指標 GOT 及 GPT 的活性較高，表示 rGSTYb1、 hGST A2 的表現並未減緩 AFB1 對肝癌細胞 Hep G2、 Hep 3B 及 Chang liver 的傷害。 rGSTYb1 選擇性的保護 Chang liver 細胞，並加速肝癌細胞 Hep G2 的死亡；而 hGST A2 則會加速 Chang liver 及 Hep 3B cell 死亡，研究結果反應不同之 GST isoforms 在不同的細胞扮演了不同的角色及生理功能。 Glutathione S-transferase (GSTs) are a family of enzymes with several functions. Although they play a role in detoxification and protection in normal liver cell, some papers reported that over-expression or down-regulation of certain GSTs might be one of the causes that lead to the formation of hepatoma or the development of drug resistance. However, it is still not clear what the relationship is between the differential expression of GST isoforms and the causes and drug resistance of hepatoma. In this study, the effects of rat GST Yb1, human GST Ya2 at the growth, the morphology change and the response to carcinogens of hepatoma cells (Hep G2, Hep 3B) and hepatocytes (Change liver) were investigated by the transient transfection system. Chang liver cells were transfected with rGSTYb1 plasmid, and then treated with AFB1. The results showed that the percentage of survival cells was higher, and the activities of GOT and GPT were lower in these cells than the vector control. There was no difference in the activities of GST alpha and GST pi between the GSTYb1-transfected cells and the vector control. The data indicated that the expression of rGSTYb1was able to protect normal hepatocytes (Chang liver cells) against the damage of AFB1. When Hep G2 and Hep 3B cells were transfected with rGSTYb1 and hGSTYa2, Chang liver cells were transfected with hGSTYa2, and then treated with AFB1, the results were opposite to that of Chang liver cells. The percentage of survival cells were lower and the activities of GOT and GPT were higher in the rGSTYb1, hGSTYa2-transfected and AFB1-treated cells than the vector control. The activities of GST alpha and GST pi were not affected by the expression of rGSTYb1 and hGSTYa2. The data indicated that the expression of rGSTYb1 and hGSTYa2 was not able to protect hepatoma cells against the damage of AFB1. In conclusion, the expression of rGSTYb1 and hGSTYa2 showed differential effects in different cell lines by protecting normal hepatocytes and, on the other hand, promoting the cells death of cancerous liver cells. Therefore, in addition to its important role in the protection function of normal liver, rGSTYb1 and hGSTYa2 might be also involved in some pathway that leads to the death of cancer cells.
URI:	https://ir.csmu.edu.tw:8080/handle/310902500/3106
Appears in Collections:	[生化微生物免疫研究所] 研究計劃

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