Yan S Y, Chen M M, Fan J G, Wang Y Q, Du Y Q, Hu Y, Xu L M
Department of Gastroenterology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Department of Pathology, Cancer Hospital, Fudan University, Shanghai, China.
Braz J Med Biol Res. 2014 Nov;47(11):947-59. doi: 10.1590/1414-431X20143808. Epub 2014 Aug 29.
This study aimed to investigate the therapeutic mechanism of treating SMMC-7721 liver cancer cells with magnetic fluid hyperthermia (MFH) using Fe₂O₃ nanoparticles. Hepatocarcinoma SMMC-7721 cells cultured in vitro were treated with ferrofluid containing Fe₂O₃ nanoparticles and irradiated with an alternating radio frequency magnetic field. The influence of the treatment on the cells was examined by inverted microscopy, MTT and flow cytometry. To study the therapeutic mechanism of the Fe₂O₃ MFH, Hsp70, Bax, Bcl-2 and p53 were detected by immunocytochemistry and reverse transcription polymerase chain reaction (RT-PCR). It was shown that Fe₂O₃ MFH could cause cellular necrosis, induce cellular apoptosis, and significantly inhibit cellular growth, all of which appeared to be dependent on the concentration of the Fe₂O₃nanoparticles. Immunocytochemistry results showed that MFH could induce high expression of Hsp70 and Bax, decrease the expression of mutant p53, and had little effect on Bcl-2. RT-PCR indicated that Hsp70 expression was high in the early stage of MFH (<24 h) and became low or absent after 24 h of MFH treatment. It can be concluded that Fe₂O₃MFH significantly inhibited the proliferation of in vitro cultured liver cancer cells (SMMC-7721), induced cell apoptosis and arrested the cell cycle at the G₂/M phase. Fe₂O₃ MFH can induce high Hsp70 expression at an early stage, enhance the expression of Bax, and decrease the expression of mutant p53, which promotes the apoptosis of tumor cells.
本研究旨在探讨利用Fe₂O₃纳米颗粒通过磁流体热疗(MFH)治疗SMMC - 7721肝癌细胞的治疗机制。体外培养的肝癌SMMC - 7721细胞用含Fe₂O₃纳米颗粒的铁磁流体处理,并施以交变射频磁场照射。通过倒置显微镜、MTT法和流式细胞术检测该处理对细胞的影响。为研究Fe₂O₃磁流体热疗的治疗机制,采用免疫细胞化学和逆转录聚合酶链反应(RT - PCR)检测Hsp70、Bax、Bcl - 2和p53。结果表明,Fe₂O₃磁流体热疗可导致细胞坏死、诱导细胞凋亡并显著抑制细胞生长,所有这些似乎都依赖于Fe₂O₃纳米颗粒的浓度。免疫细胞化学结果显示,磁流体热疗可诱导Hsp70和Bax高表达,降低突变型p53的表达,而对Bcl - 2影响较小。RT - PCR表明,磁流体热疗早期(<24 h)Hsp70表达较高,磁流体热疗处理24 h后表达降低或消失。可以得出结论,Fe₂O₃磁流体热疗显著抑制体外培养的肝癌细胞(SMMC - 7721)的增殖,诱导细胞凋亡并使细胞周期停滞在G₂/M期。Fe₂O₃磁流体热疗可在早期诱导Hsp70高表达,增强Bax表达,并降低突变型p53的表达,从而促进肿瘤细胞凋亡。