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The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy
The resistance of glioblastoma to existing therapies puts limits on quality-of-life improvements and patient survival with a glioblastoma diagnosis. The development of new effective glioblastoma therapies is based on knowledge about the mechanisms governing tumor resistance to therapeutic agents. Vi...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
A.I. Gordeyev
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307987/ https://www.ncbi.nlm.nih.gov/pubmed/35923561 http://dx.doi.org/10.32607/actanaturae.11623 |
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author | Vasileva, N. S. Ageenko, A. B. Richter, V. A. Kuligina, E. V. |
author_facet | Vasileva, N. S. Ageenko, A. B. Richter, V. A. Kuligina, E. V. |
author_sort | Vasileva, N. S. |
collection | PubMed |
description | The resistance of glioblastoma to existing therapies puts limits on quality-of-life improvements and patient survival with a glioblastoma diagnosis. The development of new effective glioblastoma therapies is based on knowledge about the mechanisms governing tumor resistance to therapeutic agents. Virotherapy is one of the most actively developing approaches to the treatment of malignant neoplasms: glioblastoma in particular. Previously, we demonstrated that the recombinant vaccinia virus VV-GMCSF-Lact exhibits in vitro cytotoxic activity and in vivo antitumor efficacy against human glioblastoma. However, the studied glioblastoma cell cultures had different sensitivities to the oncotoxic effect of the virus. In this study, we investigated cancer stem cell (CSC) surface markers in glioblastoma cells with different sensitivities to VV-GMCSFLact using flow cytometry and we assessed the levels of proteins affecting viral entry into cells and virus infection efficiency by western blotting. We showed that cell cultures more sensitive to VV-GMCSF-Lact are characterized by a greater number of cells with CSC markers and a lower level of activated Akt kinase. Akt probably inhibits lactaptin-induced apoptosis in virus-resistant cells. Hence, we suggest that the sensitivity of glioblastoma cells to the oncotoxic effect of VV-GMCSF-Lact is determined by the nature and extent of the disturbances in cell death regulation in various cultures. Further investigation of the factors affecting glioblastoma resistance to virotherapy will test this hypothesis and identify targets for antitumor therapy, combined with VV-GMCSF-Lact. |
format | Online Article Text |
id | pubmed-9307987 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | A.I. Gordeyev |
record_format | MEDLINE/PubMed |
spelling | pubmed-93079872022-08-02 The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy Vasileva, N. S. Ageenko, A. B. Richter, V. A. Kuligina, E. V. Acta Naturae Research Article The resistance of glioblastoma to existing therapies puts limits on quality-of-life improvements and patient survival with a glioblastoma diagnosis. The development of new effective glioblastoma therapies is based on knowledge about the mechanisms governing tumor resistance to therapeutic agents. Virotherapy is one of the most actively developing approaches to the treatment of malignant neoplasms: glioblastoma in particular. Previously, we demonstrated that the recombinant vaccinia virus VV-GMCSF-Lact exhibits in vitro cytotoxic activity and in vivo antitumor efficacy against human glioblastoma. However, the studied glioblastoma cell cultures had different sensitivities to the oncotoxic effect of the virus. In this study, we investigated cancer stem cell (CSC) surface markers in glioblastoma cells with different sensitivities to VV-GMCSFLact using flow cytometry and we assessed the levels of proteins affecting viral entry into cells and virus infection efficiency by western blotting. We showed that cell cultures more sensitive to VV-GMCSF-Lact are characterized by a greater number of cells with CSC markers and a lower level of activated Akt kinase. Akt probably inhibits lactaptin-induced apoptosis in virus-resistant cells. Hence, we suggest that the sensitivity of glioblastoma cells to the oncotoxic effect of VV-GMCSF-Lact is determined by the nature and extent of the disturbances in cell death regulation in various cultures. Further investigation of the factors affecting glioblastoma resistance to virotherapy will test this hypothesis and identify targets for antitumor therapy, combined with VV-GMCSF-Lact. A.I. Gordeyev 2022 /pmc/articles/PMC9307987/ /pubmed/35923561 http://dx.doi.org/10.32607/actanaturae.11623 Text en Copyright ® 2022 National Research University Higher School of Economics. https://creativecommons.org/licenses/by/2.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Vasileva, N. S. Ageenko, A. B. Richter, V. A. Kuligina, E. V. The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title_full | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title_fullStr | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title_full_unstemmed | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title_short | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
title_sort | signaling pathways controlling the efficacy of glioblastoma therapy |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9307987/ https://www.ncbi.nlm.nih.gov/pubmed/35923561 http://dx.doi.org/10.32607/actanaturae.11623 |
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