Dose enhancement effect of anticaner drugs associated with increased temperature in vitro

Istomin Yu.Р., Zhavrid E.A., Alexandrova E.N., Sergeyeva O.P., Petrovich S.V.

Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 °C or 42 °C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. Results: Hyperthermia alone caused only 10–20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. Conclusion: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect.