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

PLoS One. 2013 Sep 17;8(9):e74322. doi: 10.1371/journal.pone.0074322. eCollection 2013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / radiation effects
  • Cell Death / radiation effects
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Humans
  • Mice
  • Mitochondria / metabolism
  • NF-kappa B / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology*
  • Neoplasms / therapy
  • Neovascularization, Pathologic / metabolism
  • Neovascularization, Pathologic / therapy
  • Pulsed Radiofrequency Treatment
  • Signal Transduction*
  • Tumor Burden / radiation effects
  • Tumor Microenvironment / radiation effects
  • Wnt Proteins / metabolism*
  • beta Catenin / metabolism*

Substances

  • NF-kappa B
  • Wnt Proteins
  • beta Catenin

Grants and funding

This work was supported by the National S&T Major Project of China (2012ZX10002-017, 2012ZX10002-004), NSFC for Innovative Research Group of China (81121002), Zhejiang Medical Research Funding (2008B079, LY13H180003), SRF for ROCS, SEM (J20120279), and Xinjiang Science and Technology Bureau Project (2013911131). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.