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

被引：67

作者：

Meng, Mao-Bin ^{[1
,2
]}

Wang, Huan-Huan ^{[1
,2
]}

Guo, Wen-Hao ^{[3
,4
]}

Wu, Zhi-Qiang ^{[1
,2
]}

Zeng, Xian-Liang ^{[1
,2
]}

Zaorsky, Nicholas G. ^{[5
]}

Shi, Hua-Shan ^{[3
,4
]}

Qian, Dong ^{[1
,2
]}

Niu, Zhi-Min ^{[1
,2
]}

Jiang, Bo ^{[1
,2
]}

Zhao, Lu-Jun ^{[1
,2
]}

Yuan, Zhi-Yong ^{[1
,2
]}

Wang, Ping ^{[1
,2
]}

机构：

[1] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Dept Radiat Oncol,CyberKnife Ctr, Tianjin 300060, Peoples R China

[2] Tianjin Med Univ, Canc Inst & Hosp, Natl Clin Res Ctr Canc, Key Lab Canc Prevent & Therapy, Tianjin 300060, Peoples R China

[3] Sichuan Univ, Dept Abdominal Oncol, Ctr Canc, Chengdu 610041, Sichuan, Peoples R China

[4] Sichuan Univ, State Key Lab Biotherapy, West China Hosp, West China Clin Med Sch, Chengdu 610041, Sichuan, Peoples R China

[5] Fox Chase Canc Ctr, Dept Radiat Oncol, Philadelphia, PA 19111 USA

来源：

CANCER LETTERS | 2015年 / 356卷 / 02期

基金：

中国国家自然科学基金;

关键词：

Pyruvate kinase M2 isoform; RNA interfering; Ionizing radiation; Apoptosis; Autophagy; MALIGNANT GLIOMA-CELLS; ARSENIC TRIOXIDE; COMBINATION TREATMENT; MOLECULAR-MECHANISMS; IONIZING-RADIATION; SIGNALING PATHWAYS; INDUCED APOPTOSIS; OXIDATIVE STRESS; GENE-EXPRESSION; TUMOR-GROWTH;

D O I：

10.1016/j.canlet.2014.11.016

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 GSK3 beta 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.

引用

页码：985 / 993

页数：9

共 64 条

[1] Genes of glycolysis are ubiquitously overexpressed in 24 cancer classes [J].