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

doi:10.1186/s12967-021-02825-2

	Targeting lactate dehydrogenase a improves radiotherapy efficacy in non-small cell lung cancer: from bedside to bench
	Yang, Yang 1,2,3; Chong, Yu 4,5; Chen, Mengyuan 2,3; Dai, Wumin 3,6; Zhou, Xia 2,3; Ji, Yongling 2,3; Qiu, Guoqin 2,3; Du, Xianghui 2,3
刊名	JOURNAL OF TRANSLATIONAL MEDICINE
	2021-04-26
卷号	19
关键词	LDHA NSCLC Radiosensitivity DNA repair ROS Apoptosis
DOI	10.1186/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.
资助项目	National Natural Science Foundation of China[81702968] ; Zhejiang Province National Natural Science Foundation[LY20H160006]
WOS关键词	LDH-A ; RADIATION-THERAPY ; BREAST-CANCER ; TUMOR HYPOXIA ; GLUCOSE ; METABOLISM ; INHIBITION ; RADIOSENSITIVITY ; RESISTANCE ; EXPRESSION
WOS研究方向	Research & Experimental Medicine
语种	英语
出版者	BMC
WOS记录号	WOS:000644651300003
资助机构	National Natural Science Foundation of China ; Zhejiang Province National Natural Science Foundation
内容类型	期刊论文
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.Zhejiang Key Lab Radiat Oncol, 1 East Banshan Rd, Hangzhou 310022, Peoples R China 2.Univ Chinese Acad Sci, Dept Thorac Radiotherapy, Zhejiang Canc Hosp, Canc Hosp, Hangzhou 310022, Peoples R China 3.Chinese Acad Sci, Inst Canc & Basic Med IBMC, Hangzhou 310022, Peoples R China 4.Soochow Univ, Sch Radiol & Interdisciplinary Sci RAD X, State Key Lab Radiat Med & Protect, Suzhou 215123, Peoples R China 5.Soochow Univ, Collaborat Innovat Ctr Radiat Med Jiangsu Higher, Suzhou 215123, Peoples R China 6.Univ Chinese Acad Sci, Dept Clin Lab, Canc Hosp, 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).