Radiation biology. Radioecology
ISSN: 0869-8031

Archives → 2020 → V. 60. №5. → pp. 516–523

Article

Hyperthermia as a Method of Radiosensitization of Tumor Cells Unsusceptible to Pharmacological Radiosensitizers

A. V. Khokhlova, A. O. Yakimova, V. A. Mosina, E. I. Selivanova, and A. E. Kabakov

A. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Ministry of Health of the Russian Federation, Obninsk, Russia

Abstract

The possibility of using hyperthermia for effective radiosensitization of tumor cells with a radio- and chemoresistant phenotype was tested in an in vitro model. The work was performed on MCF-7/MDR1 cell subline originated from human breast carcinoma and demonstrating the phenomenon of multidrug resistance due to overexpression of the MDR1 gene. In comparative experiments, the maternal MCF-7 cell line was used. Cell cultures were subjected to heat stress (42–44°C, 30–90 min), then they were irradiated with γ-photons in doses of 2–8 Gy. The cytotoxicity of the treatments was evaluated in the MTT test, also on the intensity of apoptosis and necrosis, or on a decrease in clonogenicity. The transcriptional stress response of heated cells was studied in real-time PCR, determining the accumulation of mRNAs encoding inducible heat shock proteins HSP70 and HSP27. It was established that MCF-7/MDR1 radio- and chemoresistant cells do not have the increased thermoresistance, and their reactions to heat stress are comparable to those of MCF-7 cells. At the same time, it was shown that hyperthermic pretreatment significantly enhances the cytotoxic effects of γ-radiation on MCF-7/MDR1 cells; this proves the possibility of the effective use of hyperthermia for radiosensitization of radioresistant tumors which exhibit multidrug-resistance and unsusceptible to chemotherapeutic radiosensitizers. The molecular mechanisms of thermo-radiosensitization of tumor cells are here considered herein.

Keywords

transcriptional stress response, heat shock proteins, HSF1, radioresistance, MDR1, chemoresistance, cancer cells, radiation therapy