Aryl hydrocarbon receptor nuclear translocator ( ARNT )為轉錄因子，也稱作Hypoxia-inducible factor 1-β ( HIF1-β )。在缺氧下會與HIF1-α一起調控許多缺氧基因，包括了代謝與抗藥性等。實驗室先前的研究證明ARNT會調控Multidrug resistance protein 1 ( MDR1 )這個抗藥性蛋白的表現來影響癌細胞對抗癌藥物Cisplatin的抗藥性。目前，已有許多文獻表明了癌細胞的抗藥性與細胞代謝異常有關。Warburg effect為癌細胞相較於正常細胞的代謝途徑偏好從葡萄糖轉換為乳酸產生以取得能量，而不是一般由丙酮酸轉換成acetyl-CoA進入粒線體氧化磷酸化的方式。而PDK1即為Pyruvate dehydrogenase ( PDH ) 的調控者。因此，本篇探討PDK1是否受到ARNT的調控以及是否參與在ARNT所調控MDR1的表現的機制與抗藥性。從實驗結果可知，在缺乏ARNT的細胞中，PDK1的蛋白質以及RNA表現下降。另外，也證實了ARNT調控PDK1的啟動子而促進基因的轉錄活性。而在PDK1缺失的細胞也證實了MDR1的蛋白質表現下降。另外也證實了PDK1影響MDR1啟動子的表現。並在PDK1缺失的細胞中發現化療藥物誘發的細胞死亡率較高。因此，本篇證實了PDK1參與ARNT所調控MDR1的抗藥性功能。且PDK1還調控代謝上的轉換，我們的研究證實了PDK1在癌症治療上的重要性。

Aryl hydrocarbon receptor nuclear translocator ( ARNT ) is a transcription factor, also known as Hypoxia-inducible factor 1-β ( HIF1-β ). The complex of ARNT/HIF1-α regulates lots of hypoxic genes, including metabolism and drug resistance. In our previous studies we found that ARNT reduced the effect of anti-cancer drugs on tumor cell death by the regulation of MDR1 expression. The PDK1 is a Ser/Thr kinase that inactivates mitochondrial pyruvate dehydrogenase (PDH) by phosphorylation. As PDH is a gatekeeper enzyme that converts pyruvate to acetyl-CoA, PDK1 is known as a key regulator of the Warburg effect. The aim of this study is to investigate whether PDK1 is involved in ARNT-indced MDR1expression and drug resistance. Our data showed that PDK1 promoter activity, protein and mRNA expression was decreased in stable ARNT knockdown cells. In addition, MDR1 promoter activity, protein and mRNA expression were decreased in stable PDK1 knockdown cells. Furthermore, anti-cancer drug-induced cell death was increased in PDK1-silenced cancer cells. Thus, these data suggested that PDK1 may be an effective therapeutic target for cancer therapy.

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