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Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo.

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机构： [a]Department of Radiation Oncology, CyberKnife Center, and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China [b]Department of Abdominal Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Clinical Medicine School, Sichuan University, Chengdu, Sichuan 610041, China [c]Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA

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关键词： Pyruvate kinase M2 isoform RNA interfering Ionizing radiation Apoptosis Autophagy

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Aerobic glycolysis, a metabolic hallmark of cancer, is associated with radioresistance in non-small cell lung cancer (NSCLC). Pyruvate kinase M2 isoform (PKM2), a key regulator of glycolysis, is expressed exclusively in cancers. However, the impact of PKM2 silencing on the radiosensitivity of NSCLC has not been explored. Here, we show a plasmid of shRNA-PKM2 for expressing a short hairpin RNA targeting PKM2 (pshRNA-PKM2) and demonstrate that treatment with pshRNA-PKM2 effectively inhibits PKM2 expression in NSCLC cell lines and xenografts. Silencing of PKM2 expression enhanced ionizing radiation (IR)-induced apoptosis and autophagy in vitro and in vivo, accompanied by inhibiting AKT and PDK1 phosphorylation, but enhanced ERK and GSK3β phosphorylation. These results demonstrated that knockdown of PKM2 expression enhances the radiosensitivity of NSCLC cell lines and xenografts as well as may aid in the design of new therapies for the treatment of NSCLC. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

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出版当年[2015]版：

大类 | 2 区医学

小类 | 2 区肿瘤学

最新[2023]版：

大类 | 1 区

医学

小类 | 2 区肿瘤学

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第一作者机构： [a]Department of Radiation Oncology, CyberKnife Center, and Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin 300060, China

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