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...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Mashhad University of Medical Sciences
2025-01-01
|
| Series: | Iranian Journal of Basic Medical Sciences |
| Subjects: | |
| Online Access: | https://ijbms.mums.ac.ir/article_25030_9aa9a671b237daa9775399c1e0943085.pdf |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2008-3866 2008-3874 |