title: Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo.
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.
authors.affiliation: 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. Electronic address: doctormm991@hotmail.com.
authors.forename: Mao-Bin
authors.initials: MB
authors.lastname: Meng
authors.affiliation: 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.
authors.forename: Huan-Huan
authors.initials: HH
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Guo
authors.affiliation: 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.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Wu
authors.affiliation: 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.
authors.forename: Xian-Liang
authors.initials: XL
authors.lastname: Zeng
authors.affiliation: Department of Radiation Oncology, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111, USA.
authors.forename: Nicholas G
authors.initials: NG
authors.lastname: Zaorsky
authors.affiliation: 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.
authors.forename: Hua-Shan
authors.initials: HS
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Dong
authors.initials: D
authors.lastname: Qian
authors.affiliation: 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.
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Niu
authors.affiliation: 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.
authors.forename: Bo
authors.initials: B
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Lu-Jun
authors.initials: LJ
authors.lastname: Zhao
authors.affiliation: 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.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Yuan
authors.affiliation: 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.
authors.forename: Ping
authors.initials: P
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D001343:Autophagy / Q000528:radiation effects*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007124:Immunoenzyme Techniques; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D051379:Mice; D008819:Mice, Nude; D011770:Pyruvate Kinase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D011836:Radiation Tolerance / Q000235:genetics*; D011839:Radiation, Ionizing; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D011770:Pyruvate Kinase
keywords: Apoptosis; Autophagy; Ionizing radiation; Pyruvate kinase M2 isoform; RNA interfering