سامانه مدیریت نشریات علمی دانشگاه علوم پزشکی مشهد

Wang, Rouxin, Cheng, Jing, Zhang, Huanqi, Luo, Kaizhi, Wu, Rui, Li, Yangling, Zhu, Yuanheng, Zhang, Chong. (1403). Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma. , 28(1), 113-120. doi: 10.22038/ijbms.2024.79406.17200
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". , 28, 1, 1403, 113-120. doi: 10.22038/ijbms.2024.79406.17200
Wang, Rouxin, Cheng, Jing, Zhang, Huanqi, Luo, Kaizhi, Wu, Rui, Li, Yangling, Zhu, Yuanheng, Zhang, Chong. (1403). 'Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma', , 28(1), pp. 113-120. doi: 10.22038/ijbms.2024.79406.17200
Wang, Rouxin, Cheng, Jing, Zhang, Huanqi, Luo, Kaizhi, Wu, Rui, Li, Yangling, Zhu, Yuanheng, Zhang, Chong. Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma. , 1403; 28(1): 113-120. doi: 10.22038/ijbms.2024.79406.17200

Plinabulin exerts an anti-proliferative effect via the PI3K/AKT/mTOR signaling pathways in glioblastoma

Iranian Journal of Basic Medical Sciences
مقاله 14، دوره 28، شماره 1، فروردین 2025، صفحه 113-120    اصل مقاله (587.6 K)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2024.79406.17200
نویسندگان
Rouxin Wang1، 2؛ Jing Cheng1، 2؛ Huanqi Zhang1، 3؛ Kaizhi Luo2، 4؛ Rui Wu5؛ Yangling Li3؛ Yuanheng Zhu* 6؛ Chong Zhang* 2، 5
1College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China
2School of Medicine, Hangzhou City University, Hangzhou 310015, China
3Department of Clinical Pharmacology, Hangzhou First People’s Hospital, Hangzhou 310006, China
4Department of Pharmacy, Zhejiang University of Technology, Hangzhou 310027, China
5Key Laboratory of Novel Targets and Drug Study for Neural Repair of Zhejiang Province, School of Medicine, Hangzhou City University, Hangzhou 310015, China
6Department of Pharmacy, Ningbo No.2 Hospital, Ningbo 315010, China
چکیده
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.
کلیدواژه‌ها
AKT؛ Autophagy؛ EGFR؛ mTOR؛ PI3K؛ PIK3CG؛ Plinabulin
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