Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma
Objective(s): Plinabulin, a marine-derived anticancer drug targeting microtubules, exhibits anti-cancer effects on glioblastoma cells. However, its therapeutic potential, specifically for glioblastoma treatment, remains underexplored. This study aims to elucidate the mechanisms by which plinabulin e...
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Mashhad University of Medical Sciences
2025-01-01
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| Series: | Iranian Journal of Basic Medical Sciences |
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| Online Access: | https://ijbms.mums.ac.ir/article_25030_9aa9a671b237daa9775399c1e0943085.pdf |
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| author | Rouxin Wang Jing Cheng Huanqi Zhang Kaizhi Luo Rui Wu Yangling Li Yuanheng Zhu Chong Zhang |
| author_facet | Rouxin Wang Jing Cheng Huanqi Zhang Kaizhi Luo Rui Wu Yangling Li Yuanheng Zhu Chong Zhang |
| author_sort | Rouxin Wang |
| collection | DOAJ |
| description | Objective(s): Plinabulin, a marine-derived anticancer drug targeting microtubules, exhibits anti-cancer effects on glioblastoma cells. However, its therapeutic potential, specifically for glioblastoma treatment, remains underexplored. This study aims to elucidate the mechanisms by which plinabulin exerts its effects on glioblastoma cells.Materials and Methods: Using the SRB and colony formation assay to observe the effect of plinabulin on glioblastoma cell viability. Wound healing and transwell migration assay were used to test the effect of plinabulin on glioblastoma cell metastatic potential. Crucial target genes were identified through RNA sequencing and bioinformatics analysis. Protein levels were evaluated in a concentration-dependent manner using western blot analysis.Results: Plinabulin suppressed glioblastoma cell proliferation by causing cell cycle G2/M phase arrest and inhibited migration. The IC50 values were 22.20 nM in A172 cells and 20.55 nM in T98G cells. Plinabulin reduced AKT and mTOR phosphorylation. Combined with the AKT/mTOR inhibitors LY294002 and rapamycin, plinabulin decreased p-mTOR and EGFR protein levels and increased cleaved-PARP levels. Plinabulin induces autophagy, and using an autophagy inhibitor enhances plinabulin-induced cell apoptosis. This suggests that plinabulin might trigger cytoprotective autophagy in glioblastoma cells. These findings indicate that plinabulin hinders glioblastoma growth and induces protective autophagy via the PI3K/AKT/mTOR pathway. Additionally, plinabulin combined with erlotinib showed greater cytotoxic efficacy than either drug alone in glioblastoma cells in vitro.Conclusion: Our study provides new insights into the efficacy of plinabulin against glioblastoma and highlights the potential clinical utility of combining plinabulin with EGFR inhibitors as a chemotherapy strategy. |
| format | Article |
| id | doaj-art-df53dae3df39411cb9678445841995bf |
| institution | DOAJ |
| issn | 2008-3866 2008-3874 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Mashhad University of Medical Sciences |
| record_format | Article |
| series | Iranian Journal of Basic Medical Sciences |
| spelling | doaj-art-df53dae3df39411cb9678445841995bf2025-08-20T02:48:06ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-01-0128111312010.22038/ijbms.2024.79406.1720025030Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastomaRouxin Wang0Jing Cheng1Huanqi Zhang2Kaizhi Luo3Rui Wu4Yangling Li5Yuanheng Zhu6Chong Zhang7College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, ChinaSchool of Medicine, Hangzhou City University, Hangzhou 310015, ChinaKey Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, ChinaDepartment of Clinical Pharmacology, Hangzhou First People’s Hospital, Hangzhou 310006, ChinaDepartment of Pharmacy, Ningbo No.2 Hospital, Ningbo 315010, ChinaSchool of Medicine, Hangzhou City University, Hangzhou 310015, ChinaObjective(s): Plinabulin, a marine-derived anticancer drug targeting microtubules, exhibits anti-cancer effects on glioblastoma cells. However, its therapeutic potential, specifically for glioblastoma treatment, remains underexplored. This study aims to elucidate the mechanisms by which plinabulin exerts its effects on glioblastoma cells.Materials and Methods: Using the SRB and colony formation assay to observe the effect of plinabulin on glioblastoma cell viability. Wound healing and transwell migration assay were used to test the effect of plinabulin on glioblastoma cell metastatic potential. Crucial target genes were identified through RNA sequencing and bioinformatics analysis. Protein levels were evaluated in a concentration-dependent manner using western blot analysis.Results: Plinabulin suppressed glioblastoma cell proliferation by causing cell cycle G2/M phase arrest and inhibited migration. The IC50 values were 22.20 nM in A172 cells and 20.55 nM in T98G cells. Plinabulin reduced AKT and mTOR phosphorylation. Combined with the AKT/mTOR inhibitors LY294002 and rapamycin, plinabulin decreased p-mTOR and EGFR protein levels and increased cleaved-PARP levels. Plinabulin induces autophagy, and using an autophagy inhibitor enhances plinabulin-induced cell apoptosis. This suggests that plinabulin might trigger cytoprotective autophagy in glioblastoma cells. These findings indicate that plinabulin hinders glioblastoma growth and induces protective autophagy via the PI3K/AKT/mTOR pathway. Additionally, plinabulin combined with erlotinib showed greater cytotoxic efficacy than either drug alone in glioblastoma cells in vitro.Conclusion: Our study provides new insights into the efficacy of plinabulin against glioblastoma and highlights the potential clinical utility of combining plinabulin with EGFR inhibitors as a chemotherapy strategy.https://ijbms.mums.ac.ir/article_25030_9aa9a671b237daa9775399c1e0943085.pdfaktautophagyegfrmtorpi3kpik3cgplinabulin |
| spellingShingle | Rouxin Wang Jing Cheng Huanqi Zhang Kaizhi Luo Rui Wu Yangling Li Yuanheng Zhu Chong Zhang Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma Iranian Journal of Basic Medical Sciences akt autophagy egfr mtor pi3k pik3cg plinabulin |
| title | Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma |
| title_full | Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma |
| title_fullStr | Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma |
| title_full_unstemmed | Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma |
| title_short | Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma |
| title_sort | plinabulin exerts an anti proliferative effect via the pi3k akt mtor signaling pathways in glioblastoma |
| topic | akt autophagy egfr mtor pi3k pik3cg plinabulin |
| url | https://ijbms.mums.ac.ir/article_25030_9aa9a671b237daa9775399c1e0943085.pdf |
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