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热疗与电场联合治疗对非小细胞肺癌(NSCLC)细胞系的协同作用。

Synergistic effects of combined hyperthermia and electric fields treatment in non-small cell lung-cancer (NSCLC) cell lines.

作者信息

Heo Jinju, Jo Yunhui, Yoon Myonggeun

机构信息

Department of Bio-Medical Engineering, Korea University, 145 Anam-Ro, Seongbuk-Gu, Seoul, 02841, Korea.

Institute of Global Health Technology (IGHT), Korea University, Seoul, Republic of Korea.

出版信息

Clin Transl Oncol. 2025 May;27(5):2014-2023. doi: 10.1007/s12094-024-03760-6. Epub 2024 Oct 22.

Abstract

PURPOSE

Lung cancer remains a leading cause of cancer-related mortality, with non-small cell lung cancer (NSCLC) being particularly challenging due to poor survival rates, emphasizing the need for new treatments. This study examined the therapeutic effects of combining hyperthermia (HT) with tumor-treating electric fields (TTF) in NSCLC.

METHODS

Cells were exposed to four different conditions: hyperthermia at 42 °C for 30 min, electric fields at 150 kHz and 0.8 V/cm for 24 h, a combination of both treatments, or no treatment (control). Cell proliferation was measured using WST and colony-formation assays, while apoptosis, DNA damage, and repair protein levels were analyzed via Western blotting. Metastatic potential was evaluated with a transwell assay, and cell migration was assessed using the wound-healing assay.

RESULTS

The combination therapy significantly inhibited colony formation and reduced cell migration and invasion more effectively than individual treatments. The combined treatment also enhanced apoptosis, as indicated by increased cleaved-PARP and Annexin V levels. In addition, the DNA-damage marker γ-H2AX was elevated, while BRCA1, a protein involved in DNA repair, was significantly downregulated compared to the individual treatments.

CONCLUSIONS

These results suggest that the enhanced anticancer effects of HT and TTF are due to increased DNA damage and suppression of DNA-repair mechanisms, highlighting the potential of this combination therapy for NSCLC treatment.

摘要

目的

肺癌仍然是癌症相关死亡的主要原因,非小细胞肺癌(NSCLC)由于生存率低而尤其具有挑战性,这凸显了对新治疗方法的需求。本研究考察了热疗(HT)与肿瘤治疗电场(TTF)联合应用于非小细胞肺癌的治疗效果。

方法

将细胞暴露于四种不同条件下:42℃热疗30分钟、150kHz和0.8V/cm的电场处理24小时、两种治疗方法联合应用或不进行处理(对照)。使用WST和集落形成试验测量细胞增殖,同时通过蛋白质免疫印迹分析细胞凋亡、DNA损伤和修复蛋白水平。用Transwell试验评估转移潜能,用伤口愈合试验评估细胞迁移。

结果

联合治疗比单独治疗更有效地显著抑制集落形成,并减少细胞迁移和侵袭。联合治疗还增强了细胞凋亡,表现为裂解的PARP和膜联蛋白V水平升高。此外,DNA损伤标志物γ-H2AX升高,而参与DNA修复的蛋白质BRCA1与单独治疗相比显著下调。

结论

这些结果表明,热疗和肿瘤治疗电场增强的抗癌作用是由于DNA损伤增加和DNA修复机制受到抑制,突出了这种联合治疗在非小细胞肺癌治疗中的潜力。

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