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 lung cancer, which has been the leading cause of cancer death for both men and women. Erlotinib (Erl), a targeted therapy drug which triggers epidermal growth factor receptor (EGFR) pathways, has been proved to have noticeable response rate for NSCLC cells. However, it has achieved only limited treatment effect, due to intrinsic and acquired resistance among most NSCLC patients. Therefore, chemosensitizers are required to potentiate the efficacy of Erl in NSCLC treatment. The study proposed a novel thermal therapy, thermal cycling hyperthermia (TC-HT), as a supplement to amplify the effect of Erl, and proved that it can sensitize A549 NSCLC cells to Erl via the downstream of EGFR signaling cascades. In addition, we found that TC-HT not only greatly enhanced the anticancer effect of Erl but also remarkably reduced the half-maximal inhibitory concentration (IC50) to as little as 0.5 μM. Besides, via regulation of thermal dosage, TC-HT alone can produce excellent antineoplastic effect without hurting the normal cells. The method is expected to be applicable to other combination therapies and may be a starter for more sophisticated, side-effect-free anticancer treatments.