Nanosecond pulsed electric field inhibits cancer growth followed by alteration in expressions of NF-κB and Wnt/β-catenin signaling molecules.

Nanosecond pulsed electric field inhibits cancer growth followed by alteration in expressions of NF-κB and Wnt/β-catenin signaling molecules.
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纳秒脉冲电场抑制癌症生长,随后改变 NF-kappa B 和 Wnt/β-Catenin 信号分子的表达

DOI:
10.1371/journal.pone.0074322
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Zhou L
Zhou L
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Ren Z;Chen X;Cui G;Yin S;Chen L;Jiang J;Hu Z;Xie H;Zheng S;Zhou L

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癌症仍然是全球死亡的主要原因,全球病例总数正在增加。因此,迫切需要新的治疗策略来根治癌症和延长患者的生存期。一种新的技术,使用高脉冲电场已经出现从军事应用到生物学和医学,通过应用nsPEF作为一种手段,以抑制癌症。然而,nsPEF对肿瘤或癌症的分子机制仍不清楚。本研究发现nsPEF在肿瘤中具有广泛的生物学效应,并阐明了其在体内外的可能分子机制。它不仅可以通过Bcl-2家族蛋白的失衡,通过依赖线粒体的内源性凋亡途径诱导细胞凋亡,还可以通过抑制NF-κB信号通路,降低cyclin蛋白的表达,抑制细胞增殖。nsPEF还可通过抑制Wnt/β-Catenin信号通路,下调VEGF和MMPs家族蛋白的表达,从而抑制肿瘤细胞的转移和侵袭。更重要的是,nsPEF可以通过诱导肿瘤细胞凋亡、破坏肿瘤微环境和抑制肿瘤组织中的血管生成来安全有效地作为抗癌治疗。这些发现可能为癌症提供一种创造性和有效的治疗策略。
Cancer remains a leading cause of death worldwide and total number of cases globally is increasing. Novel treatment strategies are therefore desperately required for radical treatment of cancers and long survival of patients. A new technology using high pulsed electric field has emerged from military application into biology and medicine by applying nsPEF as a means to inhibit cancer. However, molecular mechanisms of nsPEF on tumors or cancers are still unclear. In this paper, we found that nsPEF had extensive biological effects in cancers, and clarified its possible molecular mechanisms in vitro and in vivo. It could not only induce cell apoptosis via dependent-mitochondria intrinsic apoptosis pathway that was triggered by imbalance of anti- or pro-apoptosis Bcl-2 family proteins, but also inhibit cell proliferation through repressing NF-κB signaling pathway to reduce expressions of cyclin proteins. Moreover, nsPEF could also inactivate metastasis and invasion in cancer cells by suppressing Wnt/β-Catenin signaling pathway to down-regulating expressions of VEGF and MMPs family proteins. More importantly, nsPEF could function safely and effectively as an anti-cancer therapy through inducing tumor cell apoptosis, destroying tumor microenvironment, and depressing angiogenesis in tumor tissue in vivo. These findings may provide a creative and effective therapeutic strategy for cancers.
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