中国比较医学杂志2025，Vol.35Issue(12)：65-75,11.DOI:10.3969/j.issn.1671-7856.2025.12.006
乔松素下调DAAM2/Wnt/β-catenin信号轴对黑色素瘤细胞凋亡和迁移的影响
Effect of pinocembrin on apoptosis and migration of melanoma cells by down-regulating DAAM2/Wnt/β-catenin signaling axis
摘要
Abstract
Objective To investigate the effect of pinocembrin(Pin)on the apoptosis and migration of mouse melanoma B16 cells,and its relationship with the disheveled-associated activator of morphogenesis 2(DAAM2)/Wnt/β-catenin signaling axis.Methods CCK8 method was used to screen the Chinese medicine monomers that could inhibit the viability of B16 cells in vitro.Cell apoptosis and migration of melanoma B16 cells were detected by flow cytometry and wound healing assay,respectively.Possible core genes of Pin were analyzed by RNA-seq sequencing combined with GEPIA database analysis.Expression levels of DAAM2 and the Wnt/β-catenin signaling pathway-related genes and proteins Axin2,phospho(p)-glycogen synthase kinase(GSK)-3β,and p-β-catenin were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR)and Western blot.Reversion experiments were performed by transfection with a DAAM2-overexpression plasmid.A mouse melanoma model was established in vivo,and the mice were then treated with low and high doses(10 mg/kg,30 mg/kg)of Pin by gavage and melanoma growth was observed.The effects of Pin on DAAM2,Axin2,β-catenin,and p-GSK3βexpression in melanoma tissues were detected by Western blot,to clarify its effect on melanoma progression.Results Pin significantly promoted apoptosis(P＜0.001)and inhibited the migration of B16 cells(P＜0.01,P＜0.001).RNA-seq and GEPIA analysis suggested that DAAM2 was a key target.Pin significantly reduced DAAM2 mRNA and protein expression,as shown by qPCR and Western blot(P＜0.05,P＜0.01,P＜0.001),and down-regulated expression levels of the Wnt/β-catenin signaling pathway-related proteins p-GSK3β,p-β-catenin,and Axin2(P＜0.001).High-dose Pin significantly inhibited melanoma growth and weight in mice in vivo,and reduced DAAM2,axin2,β-catenin,and p-GSK3β expression in tumor tissues(P＜0.05,P＜0.01),while DAAM2 overexpression reversed the effects of Pin on the DAAM2/Wnt/β-catenin signaling axis.Conclusions Pin can promote the apoptosis of melanoma cells,inhibit their migration,and inhibit melanoma growth in mice by down-regulating the DAAM2/Wnt/β-catenin signaling axis.关键词
乔松素/黑色素瘤/抗肿瘤/DAAM2/Wnt/β-cateninKey words
pinocembrin/melanoma/anti-tumor/DAAM2/Wnt/β-catenin分类
医药卫生引用本文复制引用
廖媛,王羽,贾龙浩,林婧怡,王丽..乔松素下调DAAM2/Wnt/β-catenin信号轴对黑色素瘤细胞凋亡和迁移的影响[J].中国比较医学杂志,2025,35(12):65-75,11.基金项目
西南医科大学校级项目(2024ZXYZX23) （2024ZXYZX23）
国家级大学生创新训练计划项目(202510632043). （202510632043）
