| Autor: |
Orel VE; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine.; National Technical University of Ukraine 'Igor Sikorsky Kyiv Polytechnic Institute', 16/2 Yangel Str., 03056 Kyiv, Ukraine., Diedkov AG; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine., Ostafiichuk VV; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine., Lykhova OO; R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Str., 03022 Kyiv, Ukraine., Kolesnyk DL; R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, 45 Vasylkivska Str., 03022 Kyiv, Ukraine., Orel VB; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine.; National Technical University of Ukraine 'Igor Sikorsky Kyiv Polytechnic Institute', 16/2 Yangel Str., 03056 Kyiv, Ukraine., Dasyukevich OY; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine., Rykhalskyi OY; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine., Diedkov SA; National Cancer Institute, 33/43 Zdanovska Str., 03022 Kyiv, Ukraine., Prosvietova AB; National Technical University of Ukraine 'Igor Sikorsky Kyiv Polytechnic Institute', 16/2 Yangel Str., 03056 Kyiv, Ukraine. |
| Abstrakt: |
Despite efforts in osteosarcoma (OS) research, the role of inductive moderate hyperthermia (IMH) in delivering and enhancing the antitumor effect of liposomal doxorubicin formulations (LDOX) remains unresolved. This study investigated the effect of a combination treatment with LDOX and IMH on Saos-2 human OS cells. We compared cell viability using a trypan blue assay, apoptosis and reactive oxygen species (ROS) measured by flow cytometry and pro-apoptotic Bax protein expression examined by immunocytochemistry in response to IMH (42 MHz frequency, 15 W power for 30 min), LDOX (0.4 μg/mL), and LDOX plus IMH. The lower IC 50 value of LDOX at 72 h indicated increased accumulation of the drug in the OS cells. LDOX plus IMH resulted in a 61% lower cell viability compared to no treatment. Moreover, IMH potentiated the LDOX action on the Saos-2 cells by promoting ROS production at temperatures of <42 °C. There was a 12% increase in cell populations undergoing early apoptosis with a less heterogeneous distribution of Bax after combination treatment compared to those treated with LDOX ( p < 0.05). Therefore, we determined that IMH could enhance LDOX delivery and its antitumor effect via altered membrane permeabilization, ROS generation, and a lower level of visualized Bax heterogeneity in the Saos-2 cells, suggesting the potential translation of these findings into in vivo studies. |
