1924年，德國科學家Otto Warburg提出即使在有氧的環境底下，癌細胞仍然偏好糖解作用作為能量來源，這個現象被稱為“瓦式效應”。科學家目前提出：粒線體缺陷、缺氧的環境、致癌基因的表現以及代謝酵素的改變，為造成瓦式效應的可能原因。目前，雖然可以施打子宮頸疫苗降低人類乳突病毒(HPV)的感染，但是其價格昂貴且不適合對於疫苗會過敏者，以及已經受到人類乳突病毒的感染者，因此研究治療子宮頸癌的方法仍然是必要的。另外之前的研究提出，HeLa細胞株偏好有氧呼吸作用作為能量來源，因此本實驗想要了解，檸檬酸循環中第三個酵素異檸檬酸脫氫酶(Isocitrate dehydrogenase)表現量的高低，是否會改變細胞獲取能量來源的方式，以及增加對抗癌藥物的敏感性。異檸檬酸脫氫酶分為NADP+依賴型(IDH1和IDH2)和NAD+依賴型(IDH3)，IDH3為主要執行檸檬酸循環的酵素，是一個四聚體，由兩個α次單元、一個β次單元和一個γ次單元所組成。實驗首先建立持續性沉默IDH3A表現的HeLa細胞株，其細胞型態與爬行能力和野生型HeLa細胞株並無明顯差異，對於能量的需求也沒有因此而偏向糖解作用，可能原因為p53的表現上升，導致SCO2表現量也上升，進而促進氧化磷酸化反應。於是接下來在p53缺失的H1299細胞株，也建立持續性沉默IDH3A表現的H1299細胞株，實驗結果顯示粒線體膜電位依然比野生型H1299細胞株高，因此排除p53造成促進氧化磷酸化反應的可能性。另外，持續性沉默IDH3A表現的HeLa細胞株之所以依然進行氧化磷酸化反應，是因為細胞中存在補償路徑，經由L-glutamine實驗證實此假設。實驗結果顯示持續性沉默IDH3A表現，會使得HeLa細胞株對於抗癌藥物2-DG更加敏感，並且降低其固著依賴型的生長能力。

In 1924, Otto Warburg proposed a phenomenon that cancer cells prefer using glycolysis for energy source called “Warburg effect”. Scientists present: mitochondrial defects, hypoxic environment, oncogenic signals and metabolic enzyme changes caused by“Warburg effect”for the possible mechanisms. At present, although the cervical vaccine can reduce the human papillomavirus (HPV) infection, but its price is expensive, not suitable for allergy vaccines will, and have been infected with human papillomavirus, and therefore the research of cervical cancer treatment is necessary. In addition, HeLa cell line as a preferred source of energy for aerobic respiration, so we want to understand the third of citric acid cycle enzyme isocitrate dehydrogenase the performance of high and low expression, will changes in access to energy sources of cells, as well as to increase the sensitivity of anti-cancer drugs. In mammalian tissues two additional IDH isoenzymes are present, the cytosolic NADP(+)-specific IDH1 and the mitochondrial NADP(+)-specific IDH2. The
mitochondrial NAD(+)-specific IDH3 is a heterotetramer composed of two α-subunits and single β- and γ-subunits. Then, I established IDH3A stable knockdown cell lines in HeLa cell to analyze the differences between wide type cells and stable knockdown cell lines. I found the morphology and migration ability there was no significant difference. In the demand for energy is also not biased towards the role of sugar solution, the possible reasons for the increase in p53 expression, SCO2 also lead to increased performance, and to promote the reaction of oxidative phosphorylation. So the next I established IDH3A stable knockdown cell lines in H1299 cell (p53-null), experimental results showed that mitochondrial membrane potential is still more than the height of wild-type H1299 cells, p53 is therefore excluded from the promotion of oxidative phosphorylation. Because cells exist in the compensation pathway, so the IDH3A stable knockdown cell lines still perform oxidative phosphorylation, through the L-glutamine experiments confirm this assumption. Experimental results show that the down regulation of IDH3A expression will make HeLa cell line more sensitive to
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