Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction

doi:10.1016/j.lfs.2020.118586

	Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction
	Yan, Junfang 1,2,3,4; Xie, Yi 1,3,4; Wang, Fang 1,2,3,4; Chen, Yuhong 1,2,3,4; Zhang, Jinhua 1,2,3,4; Dou, Zhihui 1,2,3,4; Gan, Lu 1,2,3,4; Li, Hongyan 1,3,4; Si, Jing 1,3,4; Sun, Chao 1,3,4
刊名	LIFE SCIENCES
	2020-12-15
卷号	263 页码:10
关键词	Mitochondrial dysfunction Carbon ion radiation Tigecycline Mitochondrial translation Akt/AMPK/mTOR pathway
ISSN号	0024-3205
DOI	10.1016/j.lfs.2020.118586
通讯作者	Zhang, Hong(zhangh@impcas.ac.cn)
英文摘要	Aims: Mitochondrial dysfunction is receiving considerable attention due to irreplaceable biological function of mitochondria. Ionizing radiation and tigecycline (TIG) alone can cause mitochondrial dysfunction, playing important role in tumor therapy. However, prior studies fail to investigate combined mechanism of carbon ion irradiation (IR) and TIG on tumor proliferation inhibition. The study aimed to explore the combined effects of both on autophagy and apoptosis. Materials and methods: NSCLC cells A549 and H1299 were treated with carbon ion, TIG, or both. Cell survival rate, autophagy, apoptosis, expression of mitochondrial signaling proteins were determined by clone formation assay, immunofluorescence of LC3B, flow cytometry and western blotting, respectively; ATP content, mitochondrial membrane potential (MMP) and Ca2+ level in mitochondria were used to assessed mitochondrial function. Key findings: Results showed IR combined TIG inhibited cells proliferation by increasing apoptosis in both cells and enhancing autophagy in H1299 cells. Additionally, combination treatment induced the most severe mitochondrial dysfunction by sharply reducing ATP, MMP and increasing Ca2+ level of mitochondria. Up -regulation and down-regulation of mitochondrial translation proteins (EF-Tu, GFM1 and MRPS12) expression affected apoptosis and autophagy, while the level of p-mTOR was consistent with their expression in both cell types. In A549 cells, p-AMPK level decreased while p-Akt and p-mTOR increased after combination treatment. Significance: Overall, our results showed that p-Akt and p-AMPK antagonistically targeted p-mTOR to regulate mitochondrial translation proteins to affect autophagy and apoptosis. Furthermore, this study suggests that combination of carbon ion and TIG is a potential therapeutic option against tumors.
资助项目	National Key Research and Development of China[2018YFE0205100] ; Key Program of the National Natural Science Foundation of China[U1632270] ; science and technology talent project in Lanzhou[2018-RC-66]
WOS研究方向	Research & Experimental Medicine ; Pharmacology & Pharmacy
语种	英语
出版者	PERGAMON-ELSEVIER SCIENCE LTD
WOS记录号	WOS:000598137300006
资助机构	National Key Research and Development of China ; Key Program of the National Natural Science Foundation of China ; science and technology talent project in Lanzhou
内容类型	期刊论文
源URL	[http://119.78.100.186/handle/113462/138547]
专题	中国科学院近代物理研究所
通讯作者	Zhang, Hong
作者单位	1.Chinese Acad Sci, Inst Modern Phys, 509 Nanchang Rd, Lanzhou 730000, Peoples R China 2.Univ Chinese Acad Sci, Grad Sch, Beijing 100039, Peoples R China 3.Key Lab Heavy Ion Radiat Med Gansu Prov, Lanzhou, Gansu, Peoples R China 4.Chinese Acad Sci, Key Lab Heavy Ion Radiat Biol & Med, Lanzhou, Gansu, Peoples R China
推荐引用方式 GB/T 7714	Yan, Junfang,Xie, Yi,Wang, Fang,et al. Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction[J]. LIFE SCIENCES,2020,263:10.
APA	Yan, Junfang.,Xie, Yi.,Wang, Fang.,Chen, Yuhong.,Zhang, Jinhua.,...&Zhang, Hong.(2020).Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction.LIFE SCIENCES,263,10.
MLA	Yan, Junfang,et al."Carbon ion combined with tigecycline inhibits lung cancer cell proliferation by inducing mitochondrial dysfunction".LIFE SCIENCES 263(2020):10.