Thermal cycling‑hyperthermia sensitizes non‑small cell lung cancer A549 cells to EGFR tyrosine kinase inhibitor erlotinib.

Abstract

Molecular targeted therapy has emerged as a mainstream treatment for non‑small cell lung cancer (NSCLC), the most common type of lung cancer and the leading cause of cancer‑related death in both men and women. Erlotinib (Erl), a targeted therapy inhibiting EGFR pathways, has shown notable response rate in NSCLC cells. However, limited efficacy of the treatment has been reported due to resistance among a proportion of patients with NSCLC. Therefore, sensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The present study proposed a novel thermal therapy, thermal cycling‑hyperthermia (TC‑HT), as a supplement to amplify the effects of Erl. It was demonstrated that TC‑HT reduced the half‑maximal inhibitory concentration of Erl to 0.5 µM and TC‑HT sensitized A549 NSCLC cells to Erl via the downstream EGFR signaling cascades. Furthermore, the combination treatment of Erl and TC‑HT induced G2/M cell cycle arrest and inhibition of cell proliferation and migration. In addition, by slightly raising the temperature of TC‑HT, TC‑HT treatment alone produced antineoplastic effects without damaging the normal IMR‑90 lung cells. The method presented in this study may be applicable to other combination therapies and could potentially act as a starter for anticancer treatments, with fewer side effects.