Wang Rouxin, Cheng Jing, Zhang Huanqi, Luo Kaizhi, Wu Rui, Li Yangling, Zhu Yuanheng, Zhang Chong
College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
School of Medicine, Hangzhou City University, Hangzhou 310015, China.
Iran J Basic Med Sci. 2025;28(1):113-120. doi: 10.22038/ijbms.2024.79406.17200.
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.
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.
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 .
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.
普利纳布林是一种源自海洋的靶向微管的抗癌药物，对胶质母细胞瘤细胞具有抗癌作用。然而，其治疗潜力，特别是对胶质母细胞瘤治疗的潜力，仍未得到充分探索。本研究旨在阐明普利纳布林对胶质母细胞瘤细胞发挥作用的机制。
使用SRB法和集落形成试验观察普利纳布林对胶质母细胞瘤细胞活力的影响。采用伤口愈合试验和Transwell迁移试验检测普利纳布林对胶质母细胞瘤细胞转移潜能的影响。通过RNA测序和生物信息学分析鉴定关键靶基因。使用蛋白质印迹分析以浓度依赖的方式评估蛋白质水平。
普利纳布林通过引起细胞周期G2/M期阻滞抑制胶质母细胞瘤细胞增殖并抑制迁移。A172细胞中的IC50值为22.20 nM，T98G细胞中的IC50值为20.55 nM。普利纳布林降低了AKT和mTOR的磷酸化水平。与AKT/mTOR抑制剂LY294002和雷帕霉素联合使用时，普利纳布林降低了p-mTOR和EGFR蛋白水平，并增加了裂解的PARP水平。普利纳布林诱导自噬，使用自噬抑制剂可增强普利纳布林诱导的细胞凋亡。这表明普利纳布林可能在胶质母细胞瘤细胞中触发细胞保护性自噬。这些发现表明，普利纳布林通过PI3K/AKT/mTOR途径阻碍胶质母细胞瘤生长并诱导保护性自噬。此外，在胶质母细胞瘤细胞中，普利纳布林与厄洛替尼联合使用显示出比单独使用任何一种药物更大的细胞毒性疗效。
我们的研究为普利纳布林对胶质母细胞瘤的疗效提供了新的见解，并突出了将普利纳布林与EGFR抑制剂联合作为化疗策略的潜在临床应用价值。
