Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma.
Nanosecond Pulsed Electric Fields Enhance the Anti-tumour Effects of the mTOR Inhibitor Everolimus against Melanoma.
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纳秒脉冲电场增强 mTOR 抑制剂依维莫司对黑色素瘤的抗肿瘤作用
DOI：
10.1038/srep39597
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发表时间：
2017-01-05
影响因子：
4.6
通讯作者：
Guo J
中科院分区：
文献类型：
--
作者：
Dai J;Wu S;Kong Y;Chi Z;Si L;Sheng X;Cui C;Fang J;Zhang J;Guo J
PI3K/mTOR/AKT通路在大多数黑色素瘤中被激活，但单独使用mTOR抑制剂对晚期黑色素瘤的活性有限。纳秒脉冲电场的应用是一种很有前途的癌症治疗方法。在这项研究中，我们评估了mTOR抑制剂伊维洛莫斯与nsPEF联合抗黑色素瘤的协同抗肿瘤效果。在nsPEF强度的同时，nsPEF和依维莫司的联合作用逐渐减少细胞生长。NsPEFS单独或联合应用可促进黑色素瘤细胞的凋亡，并伴有细胞线粒体膜电位的降低和细胞内钙离子水平的升高。活体实验表明，mTOR抑制剂evolimus和nsPEFS联合使用可提高抑制作用，nsPEFS引起的所有皮肤损伤均在1周内愈合，未见任何不良反应。联合治疗通过上调促凋亡因子Bax和下调抗凋亡因子Bcl2，诱导caspase依赖的细胞凋亡。依维莫司和nsPEF通过降低血管内皮生长因子、血管内皮生长因子受体和CD34的表达，协同抑制血管生成。我们的发现表明，nsPEFS联合mTOR抑制剂可以作为晚期黑色素瘤的一种潜在治疗方法。
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 vivoexperiments 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 pro-apoptotic 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.
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影响因子：
7.2
作者：
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通讯作者：
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影响因子：
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DOI：
10.1016/j.bbrc.2012.06.055
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影响因子：
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