Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10899739 | Cancer Letters | 2015 | 9 Pages |
Abstract
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.
Keywords
pyruvate kinase M2 isoformz-VADFACSRNA interferingphosphorylated histone 2AXPKM23-MAγ-H2AXPEP3-methyladenineAutophagyTemionizing radiationTUNELApoptosisfluorescence-activated cell sortingNSCLCNon-small cell lung cancerphosphoenolpyruvateTransmission electron microscopemicrotubule-associated protein 1 light chain 3Propidium iodide
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Authors
Mao-Bin Meng, Huan-Huan Wang, Wen-Hao Guo, Zhi-Qiang Wu, Xian-Liang Zeng, Nicholas G. Zaorsky, Hua-Shan Shi, Dong Qian, Zhi-Min Niu, Bo Jiang, Lu-Jun Zhao, Zhi-Yong Yuan, Ping Wang,