A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas
PurposeRadiation resistance significantly hinders the efficacy of radiotherapy for meningiomas, posing a primary obstacle. The clinical inadequacy of therapeutic drugs and radiosensitizers for treating meningiomas further exacerbates the challenge. Therefore, the aim of this study was to identify po...
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Frontiers Media S.A.
2025-03-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557165/full |
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| author | Jinxiu Yu Jinxiu Yu Jinxiu Yu Jiaojiao Deng Jiaojiao Deng Jiaojiao Deng Leihao Ren Leihao Ren Leihao Ren Lingyang Hua Lingyang Hua Lingyang Hua Tianqi Wu Yi Hui Chunlin Shao Ye Gong Ye Gong Ye Gong Ye Gong |
| author_facet | Jinxiu Yu Jinxiu Yu Jinxiu Yu Jiaojiao Deng Jiaojiao Deng Jiaojiao Deng Leihao Ren Leihao Ren Leihao Ren Lingyang Hua Lingyang Hua Lingyang Hua Tianqi Wu Yi Hui Chunlin Shao Ye Gong Ye Gong Ye Gong Ye Gong |
| author_sort | Jinxiu Yu |
| collection | DOAJ |
| description | PurposeRadiation resistance significantly hinders the efficacy of radiotherapy for meningiomas, posing a primary obstacle. The clinical inadequacy of therapeutic drugs and radiosensitizers for treating meningiomas further exacerbates the challenge. Therefore, the aim of this study was to identify potential radiosensitizers for treating meningiomas.MethodsA high content clonogenic survival drug screening was employed to evaluate 166 FDA-approved compounds across varied concentration ranges. Cell viability, apoptosis, and radiosensitization were assessed using CCK-8 assays, Annexin V-FITC/PI assays and standard colony formation assays. Transcriptome sequencing, immunofluorescence and cell cycle experiments were conducted to assess transcriptional profile, DNA double-strand break damage and cell cycle distribution. Finally, the radiosensitizing effect of Maytansine was assessed in vivo through subcutaneous tumor implantation in nude mice.ResultsThe proportion of maytansine exhibiting SRF≥1.5 within the detectable concentration range was 100%. CCK-8 assay indicated the IC50 values of maytansine for IOMM-Lee and CH157 were 0.26 ± 0.06 nM and 0.31 ± 0.01 nM, respectively. Standard clonogenic survival assays and Annexin V-FITC/PI assays revealed maytansine had a notable radiosensitizing effect on meningioma cells. Transcriptome sequencing analysis demonstrated that maytansine can modulate cell cycle and DNA damage repair. Immunofluorescence analysis of γ-H2AX and cell cycle experiments demonstrated that Maytansine enhances DNA double-strand breaks and induces G2/M phase arrest. Moreover, in vivo studies had indicated that Maytansine augments the therapeutic efficacy of radiotherapy.ConclusionThis study highlighted the potential of maytansine as a potent inhibitor and radiosensitizer for meningiomas by inducing G2/M phase cell cycle arrest and enhancing DNA double-strand break damage. These findings opened up a promising path in the development of radiosensitizers aimed at treating this condition. |
| format | Article |
| id | doaj-art-ce766af67e5a44b7909c9732ba2a4e2c |
| institution | OA Journals |
| issn | 1664-3224 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj-art-ce766af67e5a44b7909c9732ba2a4e2c2025-08-20T02:06:40ZengFrontiers Media S.A.Frontiers in Immunology1664-32242025-03-011610.3389/fimmu.2025.15571651557165A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomasJinxiu Yu0Jinxiu Yu1Jinxiu Yu2Jiaojiao Deng3Jiaojiao Deng4Jiaojiao Deng5Leihao Ren6Leihao Ren7Leihao Ren8Lingyang Hua9Lingyang Hua10Lingyang Hua11Tianqi Wu12Yi Hui13Chunlin Shao14Ye Gong15Ye Gong16Ye Gong17Ye Gong18Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitute of Neurosurgery, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitute of Neurosurgery, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitute of Neurosurgery, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitute of Neurosurgery, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, ChinaDepartment of Radiotherapy, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaTranslational Medical Center for Stem Cell Therapy, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, ChinaInstitute of Radiation Medicine, Shanghai Medical College, Fudan University, Shanghai, ChinaDepartment of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaInstitute of Neurosurgery, Fudan University, Shanghai, ChinaShanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Fudan University, Shanghai, ChinaDepartment of Critical Care Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, ChinaPurposeRadiation resistance significantly hinders the efficacy of radiotherapy for meningiomas, posing a primary obstacle. The clinical inadequacy of therapeutic drugs and radiosensitizers for treating meningiomas further exacerbates the challenge. Therefore, the aim of this study was to identify potential radiosensitizers for treating meningiomas.MethodsA high content clonogenic survival drug screening was employed to evaluate 166 FDA-approved compounds across varied concentration ranges. Cell viability, apoptosis, and radiosensitization were assessed using CCK-8 assays, Annexin V-FITC/PI assays and standard colony formation assays. Transcriptome sequencing, immunofluorescence and cell cycle experiments were conducted to assess transcriptional profile, DNA double-strand break damage and cell cycle distribution. Finally, the radiosensitizing effect of Maytansine was assessed in vivo through subcutaneous tumor implantation in nude mice.ResultsThe proportion of maytansine exhibiting SRF≥1.5 within the detectable concentration range was 100%. CCK-8 assay indicated the IC50 values of maytansine for IOMM-Lee and CH157 were 0.26 ± 0.06 nM and 0.31 ± 0.01 nM, respectively. Standard clonogenic survival assays and Annexin V-FITC/PI assays revealed maytansine had a notable radiosensitizing effect on meningioma cells. Transcriptome sequencing analysis demonstrated that maytansine can modulate cell cycle and DNA damage repair. Immunofluorescence analysis of γ-H2AX and cell cycle experiments demonstrated that Maytansine enhances DNA double-strand breaks and induces G2/M phase arrest. Moreover, in vivo studies had indicated that Maytansine augments the therapeutic efficacy of radiotherapy.ConclusionThis study highlighted the potential of maytansine as a potent inhibitor and radiosensitizer for meningiomas by inducing G2/M phase cell cycle arrest and enhancing DNA double-strand break damage. These findings opened up a promising path in the development of radiosensitizers aimed at treating this condition.https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557165/fullmeningiomaradiosensitivityradiotherapyhigh content clonogenic survival drug screeningmaytansin |
| spellingShingle | Jinxiu Yu Jinxiu Yu Jinxiu Yu Jiaojiao Deng Jiaojiao Deng Jiaojiao Deng Leihao Ren Leihao Ren Leihao Ren Lingyang Hua Lingyang Hua Lingyang Hua Tianqi Wu Yi Hui Chunlin Shao Ye Gong Ye Gong Ye Gong Ye Gong A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas Frontiers in Immunology meningioma radiosensitivity radiotherapy high content clonogenic survival drug screening maytansin |
| title | A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| title_full | A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| title_fullStr | A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| title_full_unstemmed | A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| title_short | A high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| title_sort | high content clonogenic survival drug screening identifies maytansine as a potent radiosensitizer for meningiomas |
| topic | meningioma radiosensitivity radiotherapy high content clonogenic survival drug screening maytansin |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2025.1557165/full |
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