a Department of Respiratory and Critical Care Medicine , The First Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
b Department of General Surgery , The Second Affiliated Hospital of Xi'an Jiaotong University , Xi'an , Shaanxi , China.
J Drug Target. 2019 Apr;27(4):460-465. doi: 10.1080/1061186X.2018.1550648. Epub 2018 Dec 4.
Recurrence of lung adenocarcinoma has become one of the most frequent causes of major cancer incidence and mortality worldwide according to its frequently gained resistance to chemotherapies. In this study, we identified a poorly-studied kinase pyruvate dehydrogenase kinase isoform 2 (PDK2) as the most up-regulated kinase encoding gene in Cisplatin resistant lung adenocarcinoma. Additionally, PDK2-dependent Cisplatin-resistance promotes tumour growth of lung adenocarcinoma both in vitro and in vivo. Clinically, PDK2 expression was up-regulated in lung adenocarcinoma and was correlated to the poor prognosis of lung cancer patients. Mechanically, PDK2 promoted cell growth and Cisplatin-resistance of lung adenocarcinoma via transcriptional regulation of cyclin and CBS domain divalent metal cation transport mediator 3 (CNNM3), indicating that PDK2-CNNM3 signalling axis could be a potential therapeutic target for Cisplatin-resistant lung adenocarcinoma.
肺癌的复发已成为全球癌症发病率和死亡率上升的主要原因之一，这主要是由于其对化疗的耐药性日益增强。在这项研究中，我们发现了一种研究较少的激酶——丙酮酸脱氢酶激酶同工酶 2（PDK2），它是顺铂耐药肺腺癌中上调最明显的编码激酶基因。此外，PDK2 依赖性顺铂耐药性促进肺腺癌在体外和体内的肿瘤生长。临床上，PDK2 的表达在肺腺癌中上调，并与肺癌患者的不良预后相关。从机制上讲，PDK2 通过转录调控细胞周期蛋白和 CBS 结构域二价金属阳离子转运介质 3（CNNM3）促进肺腺癌的细胞生长和顺铂耐药性，表明 PDK2-CNNM3 信号轴可能是顺铂耐药肺腺癌的潜在治疗靶点。
