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Diverse gastric and ovarian cancer cell response to hypethermic chemotherapy treatment in experimental setting
Date Issued |
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2021-06-03 |
Miscellaneous
Objectives Advanced gastric and ovarian neoplasms reduce life expectancy and deteriorate the quality of life. Hyperthermic intraperitoneal chemotherapy (HIPEC) potentially could improve survival; however, its effectiveness is highly variable and dependent on the tumor type. Number of clinical studies have been performed to investigate the results of HIPEC treatment, but there is a shortage of in vitro and translational studies that could give more insights into patient selection as well as technical aspects of the procedure. The aim of this study is to compare gastric and ovarian cancer cell response to hyperthermia and cisplatin treatment in experimental model. Materials and Methods OVCAR-3 (ovarian cancer) and AGS (gastric cancer) cells were exposed to cisplatin alone or combining with various temperature regimens (37 0C to 45 0C). Treatment lasted for one hour. To evaluate cell viability, MTT metabolic activity assay was used. Mass spectrometry was used to determine intracellular cisplatin concentration. Flow cytometry analyzed cellular apoptosis. Isobolograms were used to identify the relation of combined cisplatin and hyperthermia treatment. Results Hyperthermia increased intracellular cisplatin concentration in AGS cells, while in OVCAR-3 no significant change was observed. Increasing temperature reduced viability of cisplatin treated cells. At 41 0C it dropped by 8 % and 48 % in AGS and OVCAR-3 cells correspondingly. Interestingly, at 42 0C viability activation peaks were observed. As compared to 41 0C, AGS viability was increased by 47 % and OVCAR-3 by 23 %. Higher temperatures constantly decreased viability rates in both cell lines. Isobolograms showed antagonistic hyperthermia and temperature effect to both cell lines. For AGS, cisplatin caused an increase of apoptosis rate by 1.9-fold in hyperthermia only. No significant change was observed in normothermia. Cisplatin treatment increased OVCAR-3 apoptosis rates in normothermia and hyperthermia[...]