The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy
Dublin Core | PKP Metadata Items | Metadata for this Document | |
1. | Title | Title of document | The Signaling Pathways Controlling the Efficacy of Glioblastoma Therapy |
2. | Creator | Author's name, affiliation, country | Natalia S. Vasileva; Institute of Chemical Biology and Fundamental Medicine SB RAS ; Россия |
2. | Creator | Author's name, affiliation, country | Alisa B. Ageenko; Institute of Chemical Biology and Fundamental Medicine SB RAS ; Россия |
2. | Creator | Author's name, affiliation, country | Vladimir A. Richter; Institute of Chemical Biology and Fundamental Medicine SB RAS ; Россия |
2. | Creator | Author's name, affiliation, country | Elena V. Kuligina; Institute of Chemical Biology and Fundamental Medicine SB RAS ; Россия |
3. | Subject | Discipline(s) | |
3. | Subject | Keyword(s) | glioblastoma; oncolytic viruses; VV-GMCSF-Lact; cancer stem cells; mechanisms of glioblastoma resistance |
4. | Description | Abstract | 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-GMCSF-Lact 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. |
5. | Publisher | Organizing agency, location | Acta Naturae Ltd |
6. | Contributor | Sponsor(s) |
Russian Foundation for Basic Research (20-34-90041) Institute of Chemical Biology and Fundamental Medicine SB RAS (122022100238-7) |
7. | Date | (DD-MM-YYYY) | 21.07.2022 |
8. | Type | Status & genre | Peer-reviewed Article |
8. | Type | Type | Research Article |
9. | Format | File format | |
10. | Identifier | Uniform Resource Identifier | https://actanaturae.ru/2075-8251/article/view/11623 |
10. | Identifier | Digital Object Identifier (DOI) | 10.32607/actanaturae.11623 |
11. | Source | Title; vol., no. (year) | Acta Naturae; Vol 14, No 2 (2022) |
12. | Language | English=en | ru |
13. | Relation | Supp. Files |
Fig. 1. The expression profiles of CD133 and CD44 and their co-expression in MG1, BR1.20, BR3.20, U343 MG, and U87 MG cell cultures. Cell suspensions were incubated with PE-conjugated anti-CD133 and APC-conjugated anti-CD44 antibodies and analyzed by flow cytometry. The CD44-positive cell population is displayed in the upper quadrants (Q1, Q2); The CD133-positive population is represented in the right quadrants (Q2, Q3). Cells positive for both markers are presented in the upper right quadrant (Q2). The purple arrow indicates a decrease in the sensitivity of the studied cell cultures to VV-GMCSF-Lact [3] (305KB) doi: 10.32607/20758251-2022-14-2-62-70-3622 Fig. 2. Expression profiles of the CD15 and CD171 markers in U87 MG, U343 MG, BR1.20, and BR3.20 cell cultures. Cell suspensions were incubated with PE-conjugated anti-CD171 and FITC-conjugated anti-CD15 antibodies and analyzed by flow cytometry (553KB) doi: 10.32607/20758251-2022-14-2-62-70-3623 Fig. 3. Analysis of the p85α, p110α, pAKTSer473, pAKTThr308, and pPAK1Ser199/204 proteins in the cells of immortalized cultures U87 MG and U343 MG. Western blot. Lanes: K – lysates of control cells; 0.5, 1, 2, 6, and 12 h – lysates of cells incubated with VV-GMCSF-Lact for different periods of time (124KB) doi: 10.32607/20758251-2022-14-2-62-70-3624 Fig. 4. The relative levels of the p85α, p110α, pAKTSer473, pAKTThr308, and pPAK1Ser199/204 proteins in the cells of immortalized cultures U87 MG and U343 MG before and after incubation with VV-GMCSF-Lact (*p < 0.05, ** p < 0.01,*** p < 0.001) (443KB) doi: 10.32607/20758251-2022-14-2-62-70-3625 Fig. 5. Analysis of the p85α, p110α, pAKTSer473, pAKTThr308, and pPAK1Ser199/204 proteins in the cells of patient-derived cultures BR1.20 and BR3.20. Western blot. Lanes: K – lysates of control cells; 0.5, 1, 2, 6, and 12 h – lysates of cells incubated with VV-GMCSF-Lact for different periods of time (138KB) doi: 10.32607/20758251-2022-14-2-62-70-3626 Fig. 6. The relative levels of the p85α, p110α, pAKTSer473, pAKTThr308, and pPAK1Ser199/204 proteins in the cells of patient-derived cultures BR1.20 and BR3.20 before and after incubation with VV-GMCSF-Lact. ( p < 0.05) (441KB) doi: 10.32607/20758251-2022-14-2-62-70-3627 |
14. | Coverage | Geo-spatial location, chronological period, research sample (gender, age, etc.) | |
15. | Rights | Copyright and permissions |
Copyright (c) 2022 Vasileva N.S., Ageenko A.B., Richter V.A., Kuligina E.V.![]() This work is licensed under a Creative Commons Attribution 4.0 International License. |