Yang Kai-Lin, Huang Cheng-Chung, Chi Mau-Shin, Chiang Hsin-Chien, Wang Yu-Shan, Hsia Chien-Chung, Andocs Gabor, Wang Hsin-Ell, Chi Kwan-Hwa
Department of Radiation Therapy and Oncology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
Oncotarget. 2016 Dec 20;7(51):84082-84092. doi: 10.18632/oncotarget.11444.
Radiofrequency-induced hyperthermia (HT) treatments for cancer include conventional capacitive coupling hyperthermia (cCHT) and modulated electro-hyperthermia (mEHT). In this study, we directly compared these methods with regard to in vitro cytotoxicity and mechanisms of action under isothermal conditions. Hepatoma (HepG2) cells were exposed to HT treatment (42°C for 30 min) using mEHT, cCHT or a water bath. mEHT produced a much higher apoptosis rate (43.1% ± 5.8%) than cCHT (10.0% ± 0.6%), the water bath (8.4% ± 1.7%) or a 37°C control (6.6% ± 1.1%). The apoptosis-inducing effect of mEHT at 42°C was similar to that achieved with a water bath at 46°C. mEHT also increased expression of caspase-3, 8 and 9. All three hyperthermia methods increased intracellular heat shock protein 70 (Hsp70) levels, but only mEHT greatly increased the release of Hsp70 from cells. Calreticulin and E-cadherin levels in the cell membrane also increased after mEHT treatment, but not after cCHT or water bath. These results suggest that mEHT selectively deposits energy on the cell membrane and may be a useful treatment modality that targets cancer cell membranes.
用于癌症治疗的射频诱导热疗（HT）方法包括传统电容耦合热疗（cCHT）和调制式电致热疗（mEHT）。在本研究中，我们在等温条件下就体外细胞毒性和作用机制对这些方法进行了直接比较。使用mEHT、cCHT或水浴对肝癌（HepG2）细胞进行热疗处理（42°C，30分钟）。mEHT产生的凋亡率（43.1% ± 5.8%）远高于cCHT（10.0% ± 0.6%）、水浴组（8.4% ± 1.7%）或37°C对照组（6.6% ± 1.1%）。mEHT在42°C时的凋亡诱导效果与46°C水浴的效果相似。mEHT还增加了caspase-3、8和9的表达。所有三种热疗方法均提高了细胞内热休克蛋白70（Hsp70）的水平，但只有mEHT极大地增加了Hsp70从细胞中的释放。mEHT处理后细胞膜中的钙网蛋白和E-钙黏蛋白水平也有所增加，但cCHT或水浴处理后未出现这种情况。这些结果表明，mEHT能选择性地在细胞膜上沉积能量，可能是一种靶向癌细胞膜的有效治疗方式。
