Oncology Hospital of Hunan Province, Hunan, PR China.
Mol Med Rep. 2011 Jan-Feb;4(1):187-91. doi: 10.3892/mmr.2010.401. Epub 2010 Nov 30.
Hyperthermia is a promising treatment for human cervical cancer. However, little is known about whether and under what conditions heat treatment exerts tumor inhibition effects on cervical cancer, and the molecular mechanisms behind these cellular responses have yet to be elucidated. We employed the human cervical cancer cell line CaSki as a cellular model and examined the effect of cell apoptosis and proliferation under gradient thermal conditions (43, 45 and 47˚C for 40 min). Heat treatment was found to induce CaSki cell apoptosis and necrosis. Cell cycle analysis showed that cells were arrested in S phase upon the application of hyperthermia, and MTT analysis revealed that cell viability was also reduced. Of the thermal conditions, 45˚C exhibited the best induction of apoptosis, while 47˚C induced direct fierce necrosis. This was further demonstrated by examining the expression level of several key apoptosis-related genes: caspase-3, Smac and Survivin. During apoptosis, caspase-3 and Smac levels were up-regulated, whereas anti-apoptotic Survivin was down-regulated, enhancing programmed cell death. Our results reveal that heating at ≥45˚C induced cell apoptosis and necrosis, and inhibited cell proliferation at both the cellular and molecular levels. These findings support the use of hyperthermia in a clinical setting for the treatment of human cervical cancer.
热疗是一种有前途的人类宫颈癌治疗方法。然而，目前尚不清楚热疗是否以及在何种条件下对宫颈癌发挥肿瘤抑制作用，这些细胞反应背后的分子机制仍有待阐明。我们采用人宫颈癌细胞系 CaSki 作为细胞模型，研究了在梯度热条件（43、45 和 47°C 下 40 分钟）下细胞凋亡和增殖的影响。热疗诱导 CaSki 细胞凋亡和坏死。细胞周期分析显示，热疗使细胞停滞在 S 期，MTT 分析显示细胞活力也降低。在热条件中，45°C 对细胞凋亡的诱导作用最好，而 47°C 则直接导致剧烈的坏死。这通过检查几种关键的凋亡相关基因的表达水平进一步得到证实：caspase-3、Smac 和 Survivin。在细胞凋亡过程中，caspase-3 和 Smac 的水平上调，而抗凋亡的 Survivin 下调，增强了程序性细胞死亡。我们的研究结果表明，加热至≥45°C 可诱导细胞凋亡和坏死，并在细胞和分子水平上抑制细胞增殖。这些发现支持在临床环境中使用热疗治疗人类宫颈癌。
