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Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench

文献类型：期刊论文

作者Yang, Yang1,2,6; Chong, Yu4,5; Chen, Mengyuan1,6; Dai, Wumin3,6; Zhou, Xia1,6; Ji, Yongling1,6; Qiu, Guoqin1,6; Du, Xianghui1,6
刊名JOURNAL OF TRANSLATIONAL MEDICINE
出版日期2021-04-26
卷号19
关键词LDHA NSCLC Radiosensitivity DNA repair ROS Apoptosis
DOI10.1186/s12967-021-02825-2
通讯作者Yang, Yang(yangyang@zjcc.org.cn) ; Du, Xianghui(duxh@zjcc.org.cn)
英文摘要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.
WOS关键词LDH-A ; RADIATION-THERAPY ; BREAST-CANCER ; TUMOR HYPOXIA ; GLUCOSE ; METABOLISM ; INHIBITION ; RADIOSENSITIVITY ; RESISTANCE ; EXPRESSION
资助项目National Natural Science Foundation of China[81702968] ; Zhejiang Province National Natural Science Foundation[LY20H160006]
WOS研究方向Research & Experimental Medicine
语种英语
WOS记录号WOS:000644651300003
出版者BMC
资助机构National Natural Science Foundation of China ; Zhejiang Province National Natural Science Foundation
源URL[http://ir.hfcas.ac.cn:8080/handle/334002/122369]  
专题中国科学院合肥物质科学研究院
通讯作者Yang, Yang; Du, Xianghui
作者单位1.Univ Chinese Acad Sci, Dept Thorac Radiotherapy, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China
2.Zhejiang Key Lab Radiat Oncol, 1 East Banshan Rd, Hangzhou 310022, Peoples R China
3.Univ Chinese Acad Sci, Dept Clin Lab, Canc Hosp, Hangzhou 310022, Peoples R China
4.Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Suzhou 215123, Peoples R China
5.Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, State Key Lab Radiat Med & Protect, Suzhou 215123, Peoples R China
6.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Yang,Chong, Yu,Chen, Mengyuan,et al. Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench[J]. JOURNAL OF TRANSLATIONAL MEDICINE,2021,19.
APA Yang, Yang.,Chong, Yu.,Chen, Mengyuan.,Dai, Wumin.,Zhou, Xia.,...&Du, Xianghui.(2021).Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench.JOURNAL OF TRANSLATIONAL MEDICINE,19.
MLA Yang, Yang,et al."Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench".JOURNAL OF TRANSLATIONAL MEDICINE 19(2021).

入库方式： OAI收割

来源：合肥物质科学研究院

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