Nerolidol inhibits malignant biological behaviors of melanoma cells by regulating the Wnt-β-catenin pathway
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Abstract:
Objective: To investigate the molecular mechanism by which nerolidol inhibits the malignant biological behavior of melanoma A-375 and WM-115 cells through the Wnt-β-catenin pathway. Methods: Melanoma A-375 and WM-115 cells were cultured in vitro and then treated with different concentrations of nerolidol. The effects of nerolidol on the proliferation, cell cycle and apoptosis,and migration of A-375 and WM-115 cells were analyzed by SRB and clonogenic assays, FCM, Transwell, and cell scratch assays,respectively. The levels of reactive oxygen species (ROS) in the cells were examined with DCFH-DA staining. The Wnt- β -catenin pathway and the expression levels of its related downstream genes were determined by qPCR and WB. The relationship between patient prognosis and the activation of Wnt-β-catenin pathway in melanoma was analyzed using the ULCAN and GEPIA2 databases. Results:Compared with the control group, the proliferation, migration, and cell cycle of A-375 and WM-115 cells in the nerolidol-treated group were significantly inhibited (all P<0.01), while the apoptosis was significantly increased (all P<0.01); the ROS level was increased (P<0.01), and the Wnt-β-catenin pathway was inhibited, while its downstream gene expression was significantly up-regulated (P<0.01 or P<0.01). Analysis of database data showed that OS was lower in patients with high WNT1 gene expression than in patients with low expression (P<0.01). Conclusions: Nerolidol affects the Wnt-β-catenin pathway by upregulating ROS levels in A-375 andWM-115 cells, thereby inhibiting their malignant biological behaviors. The Wnt-β-catenin pathway may be a potential target for the treatment of melanoma.