Synergistic action of microwave-induced mild hyperthermia and paclitaxel in inducing apoptosis in the human breast cancer cell line MCF-7

Abstract

Microwave mild hyperthermia and paclitaxel have been reported to be involved in variety of solid tumors. However, rare related researches have been accomplished via directly killing tumor cells using thermochemotherapy. In order to clarify the potential synergy between microwave-induced hyperthermia at temperatures <41˚C and paclitaxel chemotherapy for inhibiting the growth of the human breast cancer cell line MCF-7, an MTT assay was used. The MCF-7 cells cultured in vitro were treated with paclitaxel alone, treated with microwave-induced hyperthermia for 2 h alone (at 40, 40.5 or 41˚C), or treated with a combination of paclitaxel and 2 h of hyperthermia (at 40, 40.5 or 41˚C). Flow cytometry was used to determine the cell apoptosis rate and it was demonstrated that paclitaxel decreased cell viability in a dose-dependent manner. Alone, hyperthermia for 2 h at 41˚C induced apoptosis in MCF-7 cells, to a greater extent compared with hyperthermia for 2 h at 40.0 or 40.5˚C (P<0.05). Together, paclitaxel and 2 h of hyperthermia at 40.5˚C induced significantly increased apoptosis compared with either treatment alone (P<0.05). Increasing the temperature to 41˚C in combination with paclitaxel increased the apoptotic ratio from 12.21±1.02% to 16.36±2.39%. The apoptotic ratio correlated positively with hyperthermia temperature and duration following hyperthermia, as did the synergistic effect obtained by combining hyperthermia and paclitaxel. Notably, the combination of 5 µg/ml paclitaxel and 2 h of hyperthermia at 40˚C enhanced MCF-7 cell proliferation. Mild hyperthermia may exert anti-tumor effects by inducing apoptosis, and combining hyperthermia with paclitaxel synergistically induces apoptosis. Paclitaxel dose and hyperthermia temperature require careful optimization, as low-dose paclitaxel combined with hyperthermia at an insufficient temperature may enhance breast cancer proliferation.