Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo
Targeting pyruvate kinase M2 contributes to radiosensitivity of non-small cell lung cancer cells in vitro and in vivo
复制标题
靶向丙酮酸激酶 M2 有助于非小细胞肺癌细胞体外和体内的放射敏感性
DOI：
10.1016/j.canlet.2014.11.016
复制
发表时间：
2015-01-28
期刊：
影响因子：
9.7
通讯作者：
Wang, Ping
中科院分区：
文献类型：
--
作者：
Meng, Mao-Bin;Wang, Huan-Huan;Wang, Ping
有氧糖酵解是癌症的代谢标志，与非小细胞肺癌(NSCLC)的放射抵抗有关。丙酮酸激酶M2亚型(PKM2)是糖酵解的关键调节因子，仅在癌症中表达。然而，PKM2沉默对非小细胞肺癌放射敏感性的影响尚未被探讨。在这里，我们展示了一个针对PKM2的短发夹状RNA的shRNA-PKM2表达载体(pshRNA-PKM2)，并证明了pshRNA-PKM2处理有效地抑制了PKM2在非小细胞肺癌细胞系和异种移植瘤中的表达。抑制PKM2的表达增强了电离辐射(IR)在体内外诱导的细胞凋亡和自噬，同时抑制了AKT和PDK1的磷酸化，但增强了ERK和GSK3β的磷酸化。这些结果表明，下调PKM2的表达增强了NSCLC细胞系和异种移植瘤的放射敏感性，并可能有助于设计新的治疗NSCLC的方法。(C)2014爱思唯尔爱尔兰有限公司。保留所有权利。
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.