The effect of cisplatin and hyperthermia on mitochondrial respiratory function in OVCAR-3 ovarian cancer cells

The aim of thesis. To investigate the effect of cisplatin and hyperthermia on mitochondrial respiratory functions of ovarian OVCAR-3 cancer cells. The tasks of thesis are the following. To investigate the effect of cisplatin and hyperthermia (43°C) on mitochondrial respiratory rates in ovarian cancer cells OVCAR-3; To investigate the effect of cisplatin and hyperthermia (43°C) on the mitochondrial inner and outer membrane permeability in ovarian cancer cells OVCAR-3; To evaluate the effect of hyperthermia (43°C) and cisplatin on mitochondrial respiratory rates in ovarian cancer OVCAR-3 cells. Methods. Ovarian cancer cells were divided into control and study groups treated with cisplatin (IC50 158µM) and hyperthermia (43°C). The OVCAR-3 respiratory rate of ovarian cancer cells oxidizing glutamate, malate, and succinate was recorded using the oxygraphic method. This method was performed using the Oroboros Oxygraph-2k device. Results. The study showed that cisplatin inhibited the endogenous respiratory rate of ovarian cancer cells OVCAR-3. In addition, cisplatin has been shown to inhibit the mitochondrial respiratory rates and respiratory control index in ovarian cancer OVCAR-3 cells in both conditions (normothermia and hyperthermia (43°C), oxidizing glutamate/malate), however had no effect on the mitochondrial inner membrane permeability. Cisplatin and hyperthermia (43°C) reduced succinate oxidation and increased the permeability of mitochondrial outer membrane. Conclusion. Cisplatin inhibits mitochondrial respiratory functions in all metabolic states, and single hyperthermia (43°C) had no effect on mitochondrial respiration rates in OVCAR-3 cancer cells. Cisplatin had no effect on mitochondrial inner membrane permeability, but increased the permeability of the outer mitochondrial membrane under hyperthermia (43°C). Cisplatin in combination with hyperthermia (43°C) inhibited mitochondrial respiratory rates much more as compared to cisplatin alone. Using a combination of cisplatin and hyperthermia (43°C), mitochondrial outer membrane permeability was increased in OVCAR-3 ovarian cancer cells. These data showed a synergistic effect of cisplatin and hyperthermia on mitochondrial respiratory function