Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1
Autophagy influences the low-dose hyper-radiosensitivity of human lung adenocarcinoma cells by regulating MLH1
复制标题
自噬通过调节MLH1影响人肺腺癌细胞的低剂量超放射敏感性
DOI：
10.1080/09553002.2017.1286052
复制
发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Jing Cheng
中科院分区：
文献类型：
--
作者：
Qiong Wang;Zhuya Xiao;Zhenyu Lin;Jie Zhou;Weihong Chen;Wuyun Jie;Xing Cao;Zhongyuan Yin;Jing Cheng
摘要目的：探讨自噬通过MLH 1调节对人肺腺癌细胞低剂量辐射超敏感性（HRS）的影响。材料与方法：应用免疫荧光染色、Western blotting和电镜技术检测A549和H460细胞的自噬情况。shRNA用于沉默MLH 1表达。通过实时聚合酶链反应（PCR）和Western印迹法测定MLH 1、mTOR、p-mTOR、BNIP 3和Beclin-1的水平。结果：MLH 1低表达的A549细胞表现出HRS/诱导的放射抵抗（IRR）。相反，表达高水平MLH 1的H460细胞的放射敏感性符合线性二次（LQ）模型。在下调MLH 1表达后，A549细胞表现出HRS增加和自噬抑制，而H460细胞表现出HRS/IRR。在携带MLH 1 shRNA的细胞中，mTOR、p-mTOR和BNIP 3的水平降低，mTOR/p-mTOR比率的变化反映了MLH 1表达的变化。结论：MLH 1低表达的A549细胞可能存在HRS。mTOR/p-mTOR和BNIP 3/Beclin-1信号通路均与HRS相关，但只有mTOR/p-mTOR通过MLH 1和自噬参与HRS的调控。
Abstract Purpose: To investigate the impact of autophagy on the low-dose hyper-radiosensitivity (HRS) of human lung adenocarcinoma cells via MLH1 regulation. Materials and methods: Immunofluorescent staining, Western blotting, and electron microscopy were utilized to detect autophagy in A549 and H460 cells. shRNA was used to silence MLH1 expression. The levels of MLH1, mTOR, p-mTOR, BNIP3, and Beclin-1 were measured by real-time polymerase chain reaction (PCR) and Western blotting. Results: A549 cells, which have low levels of MLH1 expression, displayed HRS/induced radioresistance (IRR). Conversely, the radiosensitivity of H460 cells, which express high levels of MLH1, conformed to the linear-quadratic (LQ) model. After down-regulating MLH1 expression, A549 cells showed increased HRS and inhibition of autophagy, whereas H460 cells exhibited HRS/IRR. The levels of mTOR, p-mTOR, and BNIP3 were reduced in cells harboring MLH1 shRNA, and the changes in the mTOR/p-mTOR ratio mirrored those in MLH1 expression. Conclusions: Low MLH1-expressing A549 cells may exhibit HRS. Both the mTOR/p-mTOR and BNIP3/Beclin-1 signaling pathways were found to be related to HRS, but only mTOR/p-mTOR is involved in the regulation of HRS via MLH1 and autophagy.
登录
查看更多内容
影响因子：
9.7
作者：
Lynn M. Martin;B. Marples;T. Lynch;D. Hollywood;L. Marignol
通讯作者：
Lynn M. Martin;B. Marples;T. Lynch;D. Hollywood;L. Marignol
DOI：
10.1016/j.ijrobp.2006.11.045
发表时间：
2007-05
期刊：
International journal of radiation oncology, biology, physics
影响因子：
--
作者：
W. Regine;N. Hanna;M. Garofalo;A. Doyle;S. Arnold;R. Kataria;J. Sims;M. Tan;M. Mohiuddin
通讯作者：
W. Regine;N. Hanna;M. Garofalo;A. Doyle;S. Arnold;R. Kataria;J. Sims;M. Tan;M. Mohiuddin
影响因子：
1.9
作者：
C. Jahraus;A. Friedman
通讯作者：
C. Jahraus;A. Friedman
DOI：
10.1667/rr1717.1
发表时间：
2009-09
期刊：
--
影响因子：
--
作者：
Lynn M. Martin;B. Marples;M. Coffey;M. Lawler;D. Hollywood;L. Marignol
通讯作者：
Lynn M. Martin;B. Marples;M. Coffey;M. Lawler;D. Hollywood;L. Marignol
影响因子：
--
作者：
N. Mazure;G. Bellot;Raquel García-Medina;D. Roux;J. Pouysségur
通讯作者：
N. Mazure;G. Bellot;Raquel García-Medina;D. Roux;J. Pouysségur