Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the   mTOR Inhibitor Everolimus against Melanoma

doi:10.1038/srep39597

CORC > 北京大学 > 工学院

	Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma
	Dai, Jie ; Wu, Shan ; Kong, Yan ; Chi, Zhihong ; Si, Lu ; Sheng, Xinan ; Cui, Chuanliang ; Fang, Jing ; Zhang, Jue ; Guo, Jun
刊名	SCIENTIFIC REPORTS
	2017
关键词	ANTICANCER AGENTS SIGNALING PATHWAY INDUCE APOPTOSIS CELL CARCINOMA CANCER-THERAPY JURKAT CELLS PHASE-II CALCIUM DEATH TRIAL
DOI	10.1038/srep39597
英文摘要	The PI3K/mTOR/AKT pathway is activated in most melanomas, but mTOR inhibitors used singly have limited activity against advanced melanomas. The application of nanosecond pulsed electric fields (nsPEFs) is a promising cancer therapy approach. In this study, we evaluated the synergistic anti-tumour efficacy of the mTOR inhibitor everolimus in conjunction with nsPEFs against melanoma. The combined treatment of nsPEFs and everolimus gradually decreased cell growth concurrent with nsPEF intensity. nsPEFs alone or combined with everolimus could promote melanoma cell apoptosis, accompanied with a loss in cellular mitochondrial membrane potential and an increase in Ca2+ levels. In vivo experiments showed that a combination of the mTOR inhibitor everolimus and nsPEFs improved the inhibitory effect, and all skin lesions caused by nsPEFs healed in 1 week without any observed adverse effect. Combination treatment induced caspase-dependent apoptosis through the upregulation of the proapoptotic factor Bax and downregulation of the anti-apoptotic factor Bcl-2. Everolimus and nsPEFs synergistically inhibited angiogenesis by decreasing the expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR), and CD34. Our findings indicate that nsPEFs in combination with an mTOR inhibitor can be used as a potential treatment approach for advanced melanoma.; Major State Basic Research Development Program of China [2013CB911004]; National Natural Science Foundation of China [81402264, 81672696]; Beijing Municipal Natural Science Foundation [7152033, 7154187]; Beijing Talents Fund [2014000021223ZK26, 2016000021223ZK18]; Beijing Baiqianwan Talents Project; Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support [ZYLX201603]; Beijing Municipal Science & Technology Commission [Z151100003915074]; Peking University Biomed-X Foundation; 985 Project of Peking University; SCI(E); ARTICLE; 7
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/475769]
专题	工学院
推荐引用方式 GB/T 7714	Dai, Jie,Wu, Shan,Kong, Yan,et al. Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma[J]. SCIENTIFIC REPORTS,2017.
APA	Dai, Jie.,Wu, Shan.,Kong, Yan.,Chi, Zhihong.,Si, Lu.,...&Guo, Jun.(2017).Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma.SCIENTIFIC REPORTS.
MLA	Dai, Jie,et al."Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma".SCIENTIFIC REPORTS (2017).