癌細胞代謝的轉換對於癌細胞的轉移和產生抗藥性中占重要的角色。丙酮酸脫氫激酶1 是代謝相關的基因之一，它的功能從氧化磷酸化轉換為糖解作用，其中參與癌細胞的生存及生長。在丙酮酸脫氫激酶1 參與抗藥性細胞的作用仍然不清楚，本篇的研究結果顯示在癌細胞中若失去丙酮酸脫氫激酶 1 再處理順鉑，會增強順鉑藥物對癌細胞株HONE-1 毒殺性。其毒殺能力是藉由增強活性氧類，來造成細胞死亡；在去除丙酮酸去氫激酶 1 的抗藥性細胞株 HONE-1-C15 ，則不透過增強活性類氧來導致抗藥性細胞死亡。同時，我們發現抗藥性細胞的粒線體膜電位及活性氧類都較原來細胞株低，並且粒線體複合物的活性在抗藥性細胞有所改變。除此之外，我們也發現抗藥性細胞的侵襲能力降低，在動物實驗觀察抗藥性細胞穿透血管能力也無改變，然而，抗藥性細胞株一旦受到藥物刺激之下，僅存活下來的細胞其轉移能力會較原本細胞株高。除此，去除丙酮酸去氫激酶 1 會增加順鉑化療藥物敏感性導致抗藥性細胞的死亡，當中的機轉至今還不清楚，日後研究方向會朝向這些抗藥性細胞，受到藥物刺激之下所存活細胞其增加轉移能力是受到哪些因素所調控。

Metabolic disorder is a hallmark of oncogenic transformation and associated with tumor metastasis and anti-cancer drug resistance. The metabolic enzyme pyruvate dehydrogenase kinase 1(PDK1) participates in tumor survival and growth through switching oxidative
phosphorylation to glycolytic metabolism. However, the effect of PDK1 on drug resistant cells in the regulation of mitochondrial reprograming remains unclear. In this study, we found that the depletion of PDK1 enhanced cisplatin-induced cell death by using cell proliferation and apoptosis assays. The knockdown of PDK1 in HONE-1 parental but not HONE-1 cisplatin resistant cells enhanced apoptosis through enhancing the reactive oxygen
species (ROS) levels. In addition, the resistant cells presented lower expression of ROS levels and mitochondrial membrane potential than parental cells. The complex activities of mitochondria were also changed in drug resistant cells. To study the metastatic properties
of resistant cells, the invasion and extravasation assays were used. We found that even reduced invasion ability in resistant cells, no changed of extravasation was observed compared to parental cells. However, the higher migration ability was observed in the survival of cisplatin-treated resistant cells. Taken together, these results suggest that PDK1 plays roles in regulation of cisplatin-induced cell death. However, the pathway that involved in PDK1-regulated cell metastasis in cisplatin-treated resistant cells remains unknown. Theincrease of invasive ability in cisplatin-treated resistant cells further suggests that external factors may contribute to initiate tumor migration.

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