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

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.