Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway
Objective(s): Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2025-04-01
|
| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_25513_56423699efec3112603c93005c6f852e.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850068316617441280 |
|---|---|
| author | Huan-Qi Zhang Dao-Ming Zhang Zhi-Zhen Huang Jing Cheng Chong Zhang Neng-Ming Lin Yang-Ling Li |
| author_facet | Huan-Qi Zhang Dao-Ming Zhang Zhi-Zhen Huang Jing Cheng Chong Zhang Neng-Ming Lin Yang-Ling Li |
| author_sort | Huan-Qi Zhang |
| collection | DOAJ |
| description | Objective(s): Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier. In this study, the antitumor effect and mechanism of vortioxetine on GBM cells were investigated.Materials and Methods: Cell proliferation in GBM cells was assessed using the CCK8 and colony formation assays. Flow cytometry, western blot, and wound healing assay were used to study the mechanisms of vortioxetine. mCherry-GFP-LC3B and confocal microscopy were used to evaluate autophagic activity. RNA sequencing uses the capabilities of high-throughput sequencing methods to provide insight into the transcriptome of cells.Results: Vortioxetine significantly inhibited the proliferation of GBM cells by inducing G1/G0 phase cell cycle arrest. Meanwhile, it also reduced the migratory capabilities of GBM cells. Furthermore, it promoted apoptotic cell death in GBM cells. In addition, it promoted autophagy in GBM cells, and autophagy inhibitors markedly enhanced its antiproliferative activities. Vortioxetine could down-regulate the expressions of PI3K and Akt, which were related to the occurrence and development of GBM. Conclusion: Our findings support the potential of vortioxetine as a novel therapeutic agent for GBM treatment. Vortioxetine exhibits anti-GBM activity via the PI3K-Akt signaling pathway. Meanwhile, our findings reveal autophagy inhibitors as an effective sensitizer for vortioxetine, offering new strategies for treating GBM. |
| format | Article |
| id | doaj-art-c09070daebf64f4d870bccd1c18d8965 |
| institution | DOAJ |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-c09070daebf64f4d870bccd1c18d89652025-08-20T02:48:06ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-04-0128441842510.22038/ijbms.2025.82513.1783625513Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathwayHuan-Qi Zhang0Dao-Ming Zhang1Zhi-Zhen Huang2Jing Cheng3Chong Zhang4Neng-Ming Lin5Yang-Ling Li6Research Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaResearch Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaResearch Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaResearch Center for Clinical Pharmacy, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaSchool of Medicine, Hangzhou City University, Hangzhou 310015, ChinaDepartment of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, ChinaDepartment of Clinical Pharmacology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou 310006, ChinaObjective(s): Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier. In this study, the antitumor effect and mechanism of vortioxetine on GBM cells were investigated.Materials and Methods: Cell proliferation in GBM cells was assessed using the CCK8 and colony formation assays. Flow cytometry, western blot, and wound healing assay were used to study the mechanisms of vortioxetine. mCherry-GFP-LC3B and confocal microscopy were used to evaluate autophagic activity. RNA sequencing uses the capabilities of high-throughput sequencing methods to provide insight into the transcriptome of cells.Results: Vortioxetine significantly inhibited the proliferation of GBM cells by inducing G1/G0 phase cell cycle arrest. Meanwhile, it also reduced the migratory capabilities of GBM cells. Furthermore, it promoted apoptotic cell death in GBM cells. In addition, it promoted autophagy in GBM cells, and autophagy inhibitors markedly enhanced its antiproliferative activities. Vortioxetine could down-regulate the expressions of PI3K and Akt, which were related to the occurrence and development of GBM. Conclusion: Our findings support the potential of vortioxetine as a novel therapeutic agent for GBM treatment. Vortioxetine exhibits anti-GBM activity via the PI3K-Akt signaling pathway. Meanwhile, our findings reveal autophagy inhibitors as an effective sensitizer for vortioxetine, offering new strategies for treating GBM.https://ijbms.mums.ac.ir/article_25513_56423699efec3112603c93005c6f852e.pdfaktapoptosisautophagygbmpi3kproliferationvortioxetine |
| spellingShingle | Huan-Qi Zhang Dao-Ming Zhang Zhi-Zhen Huang Jing Cheng Chong Zhang Neng-Ming Lin Yang-Ling Li Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway Iranian Journal of Basic Medical Sciences akt apoptosis autophagy gbm pi3k proliferation vortioxetine |
| title | Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway |
| title_full | Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway |
| title_fullStr | Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway |
| title_full_unstemmed | Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway |
| title_short | Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway |
| title_sort | vortioxetine exhibits anti glioblastoma activity via the pi3k akt signaling pathway |
| topic | akt apoptosis autophagy gbm pi3k proliferation vortioxetine |
| url | https://ijbms.mums.ac.ir/article_25513_56423699efec3112603c93005c6f852e.pdf |
| work_keys_str_mv | AT huanqizhang vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT daomingzhang vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT zhizhenhuang vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT jingcheng vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT chongzhang vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT nengminglin vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway AT yanglingli vortioxetineexhibitsantiglioblastomaactivityviathepi3kaktsignalingpathway |