異厚朴酚抑制多型性神經膠質母細胞瘤遷移的機轉研究

Glioblastoma multiform (GBM) is the most common and malignant disease in central nerve tumors. Even though patients treated with standard therapies, GBM aggressiveness causes recurrence and death in the patients owing to GBM infiltrating easily in normal brain tissue.
Honokiol, a kind of polyphenol derivative extracted from Magnolia officinalis, have antitumor, anti-angiogenesis properties in previous reports. The reports about the effect of honokiol on GBM migration are few. We evaluated that honokiol could suppress the migration of GBM U-87 MG by reorganizing actin cytoskeleton via phosphorylation of cofilin. We observed that actin filaments were reorganized to form the lamellipodia-like structure in peripheral region of cells. We used immunoblotting to detect phosphorylation of cofilin. Phosphorylated cofilin was upregulated in 1, 3, 6 hour and total cofilin moved to central region in U-87 MG. On the other hand, after treatment for 3 hours, honokiol could decrease ATP level, caused disruption of actin filament even if cofilin activity was restored after treatment for 6 hours. Finally, actin filaments were disrupted and disappeared after 24 hours. In conclusion, we found that honokiol could suppress migration via increasing the level of phospho-cofilin, losing cofilin activity, stabilizing actin filaments to form lameelipodia-like structure at early time point. At late time point, honokiol decreased ATP level and retarded actin filaments reconstruction in U-87 MG. We expected that honokiol could retard GBM tumors migration and infiltration to normal brain tissue, became an adjuvant drug in standard therapy of GBM, and improved the prognosis and extended the life of patients.