Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells

doi:10.1667/RADE-20-00145.1

	Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells
	Zhang, Fengqiu 1,2; Shao, Changsheng 2,3; Chen, Zhu 2,3; Li, Yalin 1; Jing, Xumiao 1; Huang, Qing 2,3
刊名	RADIATION RESEARCH
	2021-04-01
卷号	195
ISSN号	0033-7587
DOI	10.1667/RADE-20-00145.1
通讯作者	Huang, Qing(huangq@ipp.ac.cn)
英文摘要	Numerous studies have shown that histone deacetylase inhibitors (HDACis) improve cellular acetylation while also enhancing the radiation sensitivity. In this work, however, we confirmed that low-dose trichostatin A (TSA) as a typical HDACi could reduce rather than increase the radiosensitivity of cancer cells, while the cellular acetylation was also increased with TSA-induced epigenetic modification. The surviving fraction of HeLa/HepG2 cells pretreated with 25 nM TSA for 24 h was higher at 1 Gy/2 Gy of gamma-ray radiation than that of the cells with the same radiation dose but without TSA pretreatment. To understand the underlying mechanism, we investigated the effect of low-dose TSA on HO-1, SOD and CAT induction and activating Akt together with its downstream Nrf2 signaling pathway. Our results indicated that TSA activated HO-1, SOD and CAT expression by increasing the phosphorylation level of Nrf2 in an Akt-dependent manner. In addition, we also observed that the 25-nM-TSA-pretreated group showed a significant increase in the antioxidant capacity in terms of SOD and CAT activities. Therefore, our results suggest that low-dose TSA can activate the Akt/Nrf2 pathway and upregulate expression of HO-1, SOD and CAT to stimulate the cellular defense mechanism. This work demonstrates that low-dose TSA treatment may activate the adaptation mechanism against the oxidative stress induced by ionizing radiation, and application of HDACi treatment should be undertaken with caution to avoid its possible radioresistance in radiotherapy. (C) 2021 by Radiation Research Society
资助项目	National Natural Science Foundation of China[11635013] ; National Natural Science Foundation of China[11775272] ; National Natural Science Foundation of China[11704343] ; Key Research Project of Universities in Henan province[18A180032] ; Key Scientific and Technological Projects in Henan Province[192102310299]
WOS研究方向	Life Sciences & Biomedicine - Other Topics ; Biophysics ; Radiology, Nuclear Medicine & Medical Imaging
语种	英语
出版者	RADIATION RESEARCH SOC
WOS记录号	WOS:000636622600006
资助机构	National Natural Science Foundation of China ; Key Research Project of Universities in Henan province ; Key Scientific and Technological Projects in Henan Province
内容类型	期刊论文
源URL	[http://ir.hfcas.ac.cn:8080/handle/334002/121572]
专题	中国科学院合肥物质科学研究院
通讯作者	Huang, Qing
作者单位	1.Zhengzhou Univ, Sch Phys, Henan Key Lab Ion Beam Bioengn, Zhengzhou 450052, Peoples R China 2.Chinese Acad Sci, Inst Intelligent Machines, CAS Key Lab High Magnet Field & Ion Beam Phys Bio, HFIPS, Hefei 230031, Peoples R China 3.Univ Sci & Technol China, Sci Isl Branch, Grad Sch, Hefei 230026, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Fengqiu,Shao, Changsheng,Chen, Zhu,et al. Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells[J]. RADIATION RESEARCH,2021,195.
APA	Zhang, Fengqiu,Shao, Changsheng,Chen, Zhu,Li, Yalin,Jing, Xumiao,&Huang, Qing.(2021).Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells.RADIATION RESEARCH,195.
MLA	Zhang, Fengqiu,et al."Low Dose of Trichostatin A Improves Radiation Resistance by Activating Akt/Nrf2-Dependent Antioxidation Pathway in Cancer Cells".RADIATION RESEARCH 195(2021).