Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin
Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing...
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| Format: | Article |
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MDPI AG
2023-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/16/12833 |
| _version_ | 1797584398960295936 |
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| author | Teresa Bernardo Anna Kuntze Diana Klein Feline Heinzelmann Beate Timmermann Cläre von Neubeck |
| author_facet | Teresa Bernardo Anna Kuntze Diana Klein Feline Heinzelmann Beate Timmermann Cläre von Neubeck |
| author_sort | Teresa Bernardo |
| collection | DOAJ |
| description | Surgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing importance regarding (neo-)adjuvant and definitive anti-cancer therapies. Akin to photon-based radiotherapy, PBT is often combined with systemic treatment, such as doxorubicin (Dox). This study compares the cellular response of human microvascular endothelial cells (HMEC-1) following irradiation with photons (X) or protons (H) alone and also in combination with different sequences of Dox. The cellular survival, cell cycle, apoptosis, proliferation, viability, morphology, and migration were all investigated. Dox monotreatment had minor effects on all endpoints. Both radiation qualities alone and in combination with longer Dox schedules significantly reduced clonogenic survival and proliferation, increased the apoptotic cell fraction, induced a longer G2/M cell cycle arrest, and altered the cell morphology towards endothelial-to-mesenchymal-transition (EndoMT) processes. Radiation quality effects were seen for metabolic viability, proliferation, and motility of HMEC-1 cells. Additive effects were found for longer Dox schedules. Overall, similar effects were found for H/H-Dox and X/X-Dox. Significant alterations between the radiation qualities indicate different but not worse endothelial cell damage by H/H-Dox. |
| first_indexed | 2024-03-10T23:52:21Z |
| format | Article |
| id | doaj.art-61a2aea803d04296bcbfa50fb88ca14f |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T23:52:21Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-61a2aea803d04296bcbfa50fb88ca14f2023-11-19T01:30:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-08-0124161283310.3390/ijms241612833Endothelial Cell Response to Combined Photon or Proton Irradiation with DoxorubicinTeresa Bernardo0Anna Kuntze1Diana Klein2Feline Heinzelmann3Beate Timmermann4Cläre von Neubeck5Department of Particle Therapy, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyGerhard Domagk Institute of Pathology, University Hospital Muenster, 48149 Muenster, GermanyInstitute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyWest German Proton Therapy Centre Essen (WPE), 45147 Essen, GermanyDepartment of Particle Therapy, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanyDepartment of Particle Therapy, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, GermanySurgery, radiotherapy, and chemotherapy are essential treatment modalities to target cancer cells, but they frequently cause damage to the normal tissue, potentially leading to side effects. As proton beam radiotherapy (PBT) can precisely spare normal tissue, this therapeutic option is of increasing importance regarding (neo-)adjuvant and definitive anti-cancer therapies. Akin to photon-based radiotherapy, PBT is often combined with systemic treatment, such as doxorubicin (Dox). This study compares the cellular response of human microvascular endothelial cells (HMEC-1) following irradiation with photons (X) or protons (H) alone and also in combination with different sequences of Dox. The cellular survival, cell cycle, apoptosis, proliferation, viability, morphology, and migration were all investigated. Dox monotreatment had minor effects on all endpoints. Both radiation qualities alone and in combination with longer Dox schedules significantly reduced clonogenic survival and proliferation, increased the apoptotic cell fraction, induced a longer G2/M cell cycle arrest, and altered the cell morphology towards endothelial-to-mesenchymal-transition (EndoMT) processes. Radiation quality effects were seen for metabolic viability, proliferation, and motility of HMEC-1 cells. Additive effects were found for longer Dox schedules. Overall, similar effects were found for H/H-Dox and X/X-Dox. Significant alterations between the radiation qualities indicate different but not worse endothelial cell damage by H/H-Dox.https://www.mdpi.com/1422-0067/24/16/12833endothelial cellsproliferationmigrationcell survivalproton beam radiotherapycombined treatment |
| spellingShingle | Teresa Bernardo Anna Kuntze Diana Klein Feline Heinzelmann Beate Timmermann Cläre von Neubeck Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin International Journal of Molecular Sciences endothelial cells proliferation migration cell survival proton beam radiotherapy combined treatment |
| title | Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin |
| title_full | Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin |
| title_fullStr | Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin |
| title_full_unstemmed | Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin |
| title_short | Endothelial Cell Response to Combined Photon or Proton Irradiation with Doxorubicin |
| title_sort | endothelial cell response to combined photon or proton irradiation with doxorubicin |
| topic | endothelial cells proliferation migration cell survival proton beam radiotherapy combined treatment |
| url | https://www.mdpi.com/1422-0067/24/16/12833 |
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