能量代谢在肿瘤领域的研究日趋重要。我们首次发现双链RNA依赖的蛋白激酶PKR在肺腺癌细胞糖酵解等代谢方面有显著作用，且可通过AMPK代谢途径调控肺癌细胞生长，证实PKR可促进肺癌细胞凋亡，其高表达的肺癌患者预后较好，但具体机制未明确。我们推测PKR/AMPK可预测肺腺癌患者的预后，PKR通过降低ATP激活AMPK，进而抑制葡萄摄取及糖酵解，最终抑制蛋白质合成、促使细胞凋亡，因而可预测肺腺癌预后。我们将检测配对肺腺癌原发灶、癌旁组织、正常肺组织中PKR/AMPK及能量代谢酶的表达，明确该联合标记物在预测肺腺癌预后的价值;在此基础上采用腺病毒转染PKR建立肺腺癌过表达细胞株，研究PKR作为能量代谢关键分子引起葡萄糖代谢过程中ATP、活性氧簇、代谢酶等变化的规律，以及对AMPK的调节机制和后续能量代谢及细胞增殖变化；探讨PKR在肺腺癌中能量代谢的作用,初步探索PKR/AMPK通路靶向治疗的意义。

It is of great significance for cancer related energy metabolism. We have confirmed that Double-stranded RNA-dependent protein kinase (PKR) is an independent prognostic variable in patients with non–small cell lung cancer (NSCLC),which can inhibit the protein synthesis and promote the apoptosis. On the other hands, We previously found PKR plays an essential role in glycolysis and regulates AMP-activated protein kinase (AMPK) signal pathway. What’s more important, we found that PKR up regulated p-AMPK Thr172 and p-AMPK Ser485, down regulated total AMPK, inducing the appearance of multiple, phosphatase-sensitive, low-mobility forms of the AMPK α-subunit. As a result, we suppose that PKR/AMPK can predict the prognosis of lung adenocarcinoma as a combined metabolism related biomarkers; PKR can activate AMPK by inhibiting ATP/AMP ratio, resulting in inhibiting cellular glucose uptake and lactate level. This is the reason why PKR can inhibit protein synthesis and promote the apoptosis of lung cancer cells. We plan to explore the PKR/AMPK expression and Metabolic enzymes expressions in the paired primary lung adenocarcinoma tissues, tumor-adjacent tissues and normal lung tissues. Then we explore the glucose uptake, lactate and ATP level, ROS expression in adeno-virus transfected PKR in lung adenocarcinoma cells. At last we try to confirm the directly and indirectly mechanism of activation of AMPK by the PKR and the effect of energy metabolism values. We aim to confirm the target value and mechanism of PKR/AMPK pathway in the effect of engery metabolism of lung adenocarcinoma.