Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, Tokyo, 162-8666, Japan.
Department of Mechanical Engineering, Keio University, Yokohama, 223-8522, Japan.
Sci Rep. 2021 Nov 2;11(1):21466. doi: 10.1038/s41598-021-00908-0.
Hyperthermia has been studied as a noninvasive cancer treatment. Cancer cells show stronger thermal cytotoxicity than normal cells, which is exploited in hyperthermia. However, the absence of methods evaluating the thermal cytotoxicity in cells prevents the development of hyperthermia. To investigate the thermal cytotoxicity, culture temperature should be regulated. We, thus, developed a culture system regulating culture temperature immediately and accurately by employing metallic culture vessels. Michigan Cancer Foundation-7 cells and normal human dermal fibroblasts were used for models of cancer and normal cells. The findings showed cancer cells showed stronger thermal cytotoxicity than normal cells, which is quantitatively different from previous reports. This difference might be due to regulated culture temperature. The thermal stimulus condition (43 °C/30 min) was, further, focused for assays. The mRNA expression involving apoptosis changed dramatically in cancer cells, indicating the strong apoptotic trend. In contrast, the mRNA expression of heat shock protein (HSP) of normal cells upon the thermal stimulus was stronger than cancer cells. Furthermore, exclusively in normal cells, HSP localization to nucleus was confirmed. These movement of HSP confer thermotolerance to cells, which is consistent with the different thermal cytotoxicity between cancer and normal cells. In summary, our developed system can be used to develop hyperthermia treatment.
热疗已被研究为一种非侵入性的癌症治疗方法。癌细胞比正常细胞表现出更强的热细胞毒性,这在热疗中得到了利用。然而,缺乏评估细胞热细胞毒性的方法阻碍了热疗的发展。为了研究热细胞毒性,应该调节培养温度。因此,我们通过使用金属培养容器开发了一种能够立即且精确地调节培养温度的培养系统。密歇根癌症基金会-7 细胞和正常人皮肤成纤维细胞被用作癌细胞和正常细胞的模型。研究结果表明,癌细胞比正常细胞表现出更强的热细胞毒性,这在数量上与以前的报告不同。这种差异可能是由于调节培养温度所致。进一步聚焦于热刺激条件(43°C/30min)进行分析。涉及凋亡的 mRNA 表达在癌细胞中发生显著变化,表明存在强烈的凋亡趋势。相比之下,正常细胞在热刺激下热休克蛋白 (HSP) 的 mRNA 表达强于癌细胞。此外,仅在正常细胞中,确证了 HSP 定位到细胞核。HSP 的这种运动赋予细胞耐热性,这与癌细胞和正常细胞之间不同的热细胞毒性一致。总之,我们开发的系统可用于开发热疗。