Hyperthermia and Chemotherapy Combination in Triple-Negative Breast Cancer Cells

Breast cancer remains the most prevalent cancer among women worldwide and a major contributor to cancer-related mortality. Among its subtypes, triple-negative breast cancer (TNBC) is particularly aggressive, with limited therapeutic options and poor survival outcomes. In this study, we investigated the cytotoxic effects of hyperthermia in combination with the chemotherapeutic agents paclitaxel (PTX) and doxorubicin (DOX) in the TNBC cell line MDA-MB-231. Hyperthermia combined with PTX or DOX significantly reduced cell viability compared to the isolated treatments (p < 0.05). The combination with DOX was the most effective, with a 30% greater inhibition of viability compared to DOX alone. Notably, cells treated with 0.04 µM DOX plus hyperthermia (43 °C, 60 min) achieved 47.1 ± 6.8% viability, whereas 0.2 µM DOX alone at 37 °C reduced viability to 52.4 ± 5.0%, representing a fourfold lower drug dose for similar efficacy (Dose reduction index of 5.7). Mechanistic studies revealed that combined treatments impaired cell cycle progression, increased reactive oxygen species (ROS) production, and induced apoptosis. Overall, our findings demonstrate that hyperthermia is a promising adjuvant to enhance the efficacy of PTX and DOX in TNBC cells, potentially reducing required drug doses and associated side effects.