Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench
Abstract Background Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiother...
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doaj-7da063b383df45bfaa7f13070f058e832021-05-02T11:11:51ZengBMCJournal of Translational Medicine1479-58762021-04-0119111410.1186/s12967-021-02825-2Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to benchYang Yang0Yu Chong1Mengyuan Chen2Wumin Dai3Xia Zhou4Yongling Ji5Guoqin Qiu6Xianghui Du7Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)State Key Laboratory of Radiation Medicine and Protection, School for Radiological and Interdisciplinary Sciences (RAD-X), and Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, Soochow UniversityDepartment of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Cancer and Basic Medicine (IBMC), Chinese Academy of SciencesDepartment of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Department of Thoracic Radiotherapy, Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Abstract Background Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. Methods LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan–Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. Results Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. Conclusions Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials.https://doi.org/10.1186/s12967-021-02825-2LDHANSCLCRadiosensitivityDNA repairROSApoptosis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yang Yang Yu Chong Mengyuan Chen Wumin Dai Xia Zhou Yongling Ji Guoqin Qiu Xianghui Du |
spellingShingle |
Yang Yang Yu Chong Mengyuan Chen Wumin Dai Xia Zhou Yongling Ji Guoqin Qiu Xianghui Du Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench Journal of Translational Medicine LDHA NSCLC Radiosensitivity DNA repair ROS Apoptosis |
author_facet |
Yang Yang Yu Chong Mengyuan Chen Wumin Dai Xia Zhou Yongling Ji Guoqin Qiu Xianghui Du |
author_sort |
Yang Yang |
title |
Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
title_short |
Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
title_full |
Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
title_fullStr |
Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
title_full_unstemmed |
Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
title_sort |
targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench |
publisher |
BMC |
series |
Journal of Translational Medicine |
issn |
1479-5876 |
publishDate |
2021-04-01 |
description |
Abstract Background Lactate dehydrogenase A (LDHA) is overexpressed and associated with poor prognosis in many kinds of cancer. In the current study, we evaluated the prognostic value of LDHA expression in non-small cell lung cancer (NSCLC), and tested whether LDHA inhibition might improve radiotherapy efficacy in NSCLC. Methods LDHA expression was investigated in NSCLC patients, using online database and further verified by immunohistochemistry. The prognostic value of LDHA was evaluated using Kaplan–Meier plotter database. In vitro, two NSCLC cell lines were pretreated with oxamate, an inhibitor of LDHA, and colony formation method was performed to determine cellular radiosensitivity. Comet assay was used to detect DNA damage after irradiation. Flow cytometry was applied to test cell cycle progression and apoptosis, and monodansylcadaverine (MDC) staining was used to examine cell autophagy. Results Both mRNA and protein levels of LDHA expression were up-regulated in NSCLC tissues. High LDHA expression was a poor prognostic factor and associated with radioresistance in NSCLC patients. LDHA inhibition by oxamate remarkably increased radiosensitivity in both A549 and H1975 cancer cells, and enhanced ionizing radiation (IR)-induced apoptosis and autophagy, accompanied by cell cycle distribution alternations. Furthermore, LDHA inhibition induced reactive oxygen species (ROS) accumulation and cellular ATP depletion, which might increase DNA injury and hinder DNA repair activity. Conclusions Our study suggests that inhibition of LDHA may be a potential strategy to improve radiotherapy efficacy in NSCLC patients, which needs to be further tested by clinical trials. |
topic |
LDHA NSCLC Radiosensitivity DNA repair ROS Apoptosis |
url |
https://doi.org/10.1186/s12967-021-02825-2 |
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