Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma
Although Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, res...
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MDPI AG
2023-05-01
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author | Andreas Nitsch Sara Qarqash Sarah Römer Janosch Schoon Axel Ekkernkamp Maya Niethard Johannes C. Reichert Georgi I. Wassilew Mladen V. Tzvetkov Lyubomir Haralambiev |
author_facet | Andreas Nitsch Sara Qarqash Sarah Römer Janosch Schoon Axel Ekkernkamp Maya Niethard Johannes C. Reichert Georgi I. Wassilew Mladen V. Tzvetkov Lyubomir Haralambiev |
author_sort | Andreas Nitsch |
collection | DOAJ |
description | Although Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC<sub>20</sub> and IC<sub>50</sub> were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine. |
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spelling | doaj.art-c34b49000221400c8a11457b85c61a9b2023-11-18T01:39:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-012410866910.3390/ijms24108669Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical PlasmaAndreas Nitsch0Sara Qarqash1Sarah Römer2Janosch Schoon3Axel Ekkernkamp4Maya Niethard5Johannes C. Reichert6Georgi I. Wassilew7Mladen V. Tzvetkov8Lyubomir Haralambiev9Center for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyDepartment of General Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, 17487 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyDepartment of General Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C_DAT), University Medicine Greifswald, 17487 Greifswald, GermanyCenter for Orthopedics, Trauma Surgery and Rehabilitation Medicine, University Medicine Greifswald, Ferdinand-Sauerbruch-Straße, 17475 Greifswald, GermanyAlthough Ewing’s sarcoma (ES) is a rare, but very aggressive tumor disease affecting the musculoskeletal system, especially in children, it is very aggressive and difficult to treat. Although medical advances and the establishment of chemotherapy represent a turning point in the treatment of ES, resistance to chemotherapy, and its side effects, continue to be problems. New treatment methods such as the application of cold physical plasma (CPP) are considered potential supporting tools since CPP is an exogenous source of reactive oxygen and nitrogen species, which have similar mechanisms of action in the tumor cells as chemotherapy. This study aims to investigate the synergistic effects of CPP and commonly used cytostatic chemotherapeutics on ES cells. The chemotherapy drugs doxorubicin and vincristine, the most commonly used in the treatment of ES, were applied to two different ES cell lines (RD-ES and A673) and their IC<sub>20</sub> and IC<sub>50</sub> were determined. In addition, individual chemotherapeutics in combination with CPP were applied to the ES cells and the effects on cell growth, cell viability, and apoptosis processes were examined. A single CPP treatment resulted in the dose-dependent growth inhibition of ES cells. The combination of different cytostatics and CPP led to significant growth inhibition, a reduction in cell viability, and higher rates of apoptosis compared to cells not additionally exposed to CPP. The combination of CPP treatment and the application of cytostatic drugs to ES cells showed promising results, significantly enhancing the cytotoxic effects of chemotherapeutic agents. These preclinical in vitro data indicate that the use of CPP can enhance the efficacy of common cytostatic chemotherapeutics, and thus support the translation of CPP as an anti-tumor therapy in clinical routine.https://www.mdpi.com/1422-0067/24/10/8669Ewing sarcomachemotherapycold physical plasmadoxorubicinvincristine |
spellingShingle | Andreas Nitsch Sara Qarqash Sarah Römer Janosch Schoon Axel Ekkernkamp Maya Niethard Johannes C. Reichert Georgi I. Wassilew Mladen V. Tzvetkov Lyubomir Haralambiev Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma International Journal of Molecular Sciences Ewing sarcoma chemotherapy cold physical plasma doxorubicin vincristine |
title | Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma |
title_full | Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma |
title_fullStr | Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma |
title_full_unstemmed | Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma |
title_short | Enhancing the Impact of Chemotherapy on Ewing Sarcoma Cells through Combination with Cold Physical Plasma |
title_sort | enhancing the impact of chemotherapy on ewing sarcoma cells through combination with cold physical plasma |
topic | Ewing sarcoma chemotherapy cold physical plasma doxorubicin vincristine |
url | https://www.mdpi.com/1422-0067/24/10/8669 |
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