Servicio Investigación-BEM, IRYCIS, Hospital Ramón y Cajal, 28034 Madrid, Spain.
Int J Oncol. 2010 Dec;37(6):1399-405.
The capacitive-resistive electric transfer (CRet) therapy is a non-invasive technique that applies electrical currents of 0.4-0.6 MHz to the treatment of musculoskeletal injuries. Although this therapy has proved effective in clinical studies, its interaction mechanisms at the cellular level still are insufficiently investigated. Results from previous studies have shown that the application of CRet currents at subthermal doses causes alterations in cell cycle progression and decreased proliferation in hepatocarcinoma (HepG2) and neuroblastoma (NB69) human cell lines. The aim of the present study was to investigate the antiproliferative response of HepG2 to CRet currents. The results showed that 24-h intermittent treatment with 50 µA/mm(2) current density induced in HepG2 statistically significant changes in expression and activation of cell cycle control proteins p27Kip1 and cyclins D1, A and B1. The chronology of these changes is coherent with that of the alterations reported in the cell cycle of HepG2 when exposed to the same electric treatment. We propose that the antiproliferative effect exerted by the electric stimulus would be primarily mediated by changes in the expression and activation of proteins intervening in cell cycle regulation, which are among the targets of emerging chemical therapies. The capability to arrest the cell cycle through electrically-induced changes in cell cycle control proteins might open new possibilities in the field of oncology.
电容电阻电转移 (CRet) 疗法是一种非侵入性技术，它应用 0.4-0.6 MHz 的电流治疗肌肉骨骼损伤。尽管这种疗法已在临床研究中被证明有效，但它在细胞水平上的相互作用机制仍未得到充分研究。先前的研究结果表明，亚热剂量的 CRet 电流应用会导致肝癌 (HepG2) 和神经母细胞瘤 (NB69) 人细胞系细胞周期进程改变和增殖减少。本研究旨在研究 HepG2 对 CRet 电流的抗增殖反应。结果表明，以 50 µA/mm(2) 电流密度进行 24 小时间歇性处理会导致 HepG2 中细胞周期控制蛋白 p27Kip1 和细胞周期蛋白 D1、A 和 B1 的表达和激活发生统计学上显著变化。这些变化的时间顺序与 HepG2 暴露于相同电处理时细胞周期中的变化一致。我们提出，电刺激施加的抗增殖作用主要是通过细胞周期调控蛋白的表达和激活变化介导的，这些蛋白是新兴化学疗法的靶标之一。通过细胞周期控制蛋白的电诱导变化来阻止细胞周期的能力可能为肿瘤学领域开辟新的可能性。
