Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids
<b>Background:</b> Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple...
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MDPI AG
2025-07-01
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| author | Kesara Nittayaboon Piyatida Molika Rassanee Bissanum Kittinun Leetanaporn Nipha Chumsuwan Raphatphorn Navakanitworakul |
| author_facet | Kesara Nittayaboon Piyatida Molika Rassanee Bissanum Kittinun Leetanaporn Nipha Chumsuwan Raphatphorn Navakanitworakul |
| author_sort | Kesara Nittayaboon |
| collection | DOAJ |
| description | <b>Background:</b> Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple roles in tumorigenesis, angiogenesis, and metastasis. BM-MSC-derived exosomes (BM-MSCs-exo) are small vesicles, typically 50–300 nm in diameter, isolated from BM-MSCs. Some studies have demonstrated the tumor-suppressive effects of BM-MSCs-exo. <b>Objective:</b> This study aimed to investigate their role in modulating the impact of chemoradiotherapy (CRT) in different types of cervical cancer spheroid cells. <b>Methods:</b> The spheroids after treatment were subject to size measurement, cell viability, and caspase activity. Then, the molecular mechanism was elucidated by Western blot analysis. <b>Results:</b> We observed a reduction in spheroid size and an increase in cell death in HeLa spheroids, while no significant changes in size or cell viability were found in SiHa spheroids. At the molecular level, CRT treatment combined with BM-MSCs-exo in HeLa spheroids induced apoptosis through the activation of the NF-κB pathway, specifically via the NF-κB1 (P50) transcription factor, leading to the upregulation of apoptosis-related molecules. In contrast, CRT combined with BM-MSCs-exo in SiHa spheroids exhibited an opposing effect: although cellular viability decreased, caspase activity also decreased, which correlated with increased HSP27 expression and the subsequent downregulation of apoptotic molecules. <b>Conclusion:</b> Our study provides deeper insight into the potential of BM-MSCs-exo in cervical cancer treatment, supporting the development of more effective and safer therapeutic strategies for clinical application. |
| format | Article |
| id | doaj-art-10f7599e9b7c4d0aa7f687d893373971 |
| institution | DOAJ |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-10f7599e9b7c4d0aa7f687d8933739712025-08-20T03:07:58ZengMDPI AGPharmaceuticals1424-82472025-07-01187105010.3390/ph18071050Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer SpheroidsKesara Nittayaboon0Piyatida Molika1Rassanee Bissanum2Kittinun Leetanaporn3Nipha Chumsuwan4Raphatphorn Navakanitworakul5Department of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, ThailandDepartment of Radiology, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, ThailandDepartment of Biomedical Sciences and Biomedical Engineering, Faculty of Medicine, Prince of Songkla University, Hat Yai 90110, Thailand<b>Background:</b> Bone marrow mesenchymal stem cells (BM-MSCs) are significant in chemo- and radiotherapy resistance. Previous research has focused on BM-MSCs, demonstrating their functional involvement in cancer progression as mediators in the tumor microenvironment. They play multiple roles in tumorigenesis, angiogenesis, and metastasis. BM-MSC-derived exosomes (BM-MSCs-exo) are small vesicles, typically 50–300 nm in diameter, isolated from BM-MSCs. Some studies have demonstrated the tumor-suppressive effects of BM-MSCs-exo. <b>Objective:</b> This study aimed to investigate their role in modulating the impact of chemoradiotherapy (CRT) in different types of cervical cancer spheroid cells. <b>Methods:</b> The spheroids after treatment were subject to size measurement, cell viability, and caspase activity. Then, the molecular mechanism was elucidated by Western blot analysis. <b>Results:</b> We observed a reduction in spheroid size and an increase in cell death in HeLa spheroids, while no significant changes in size or cell viability were found in SiHa spheroids. At the molecular level, CRT treatment combined with BM-MSCs-exo in HeLa spheroids induced apoptosis through the activation of the NF-κB pathway, specifically via the NF-κB1 (P50) transcription factor, leading to the upregulation of apoptosis-related molecules. In contrast, CRT combined with BM-MSCs-exo in SiHa spheroids exhibited an opposing effect: although cellular viability decreased, caspase activity also decreased, which correlated with increased HSP27 expression and the subsequent downregulation of apoptotic molecules. <b>Conclusion:</b> Our study provides deeper insight into the potential of BM-MSCs-exo in cervical cancer treatment, supporting the development of more effective and safer therapeutic strategies for clinical application.https://www.mdpi.com/1424-8247/18/7/1050bone marrow mesenchymal stem cells (BM-MSCs)exosomescervical cancercancer therapychemo- and radiotherapy resistance |
| spellingShingle | Kesara Nittayaboon Piyatida Molika Rassanee Bissanum Kittinun Leetanaporn Nipha Chumsuwan Raphatphorn Navakanitworakul Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids Pharmaceuticals bone marrow mesenchymal stem cells (BM-MSCs) exosomes cervical cancer cancer therapy chemo- and radiotherapy resistance |
| title | Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids |
| title_full | Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids |
| title_fullStr | Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids |
| title_full_unstemmed | Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids |
| title_short | Bone Marrow Mesenchymal Stem Cell-Derived Exosomes Modulate Chemoradiotherapy Response in Cervical Cancer Spheroids |
| title_sort | bone marrow mesenchymal stem cell derived exosomes modulate chemoradiotherapy response in cervical cancer spheroids |
| topic | bone marrow mesenchymal stem cells (BM-MSCs) exosomes cervical cancer cancer therapy chemo- and radiotherapy resistance |
| url | https://www.mdpi.com/1424-8247/18/7/1050 |
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