龙葵碱通过拮抗Wnt/β-连环蛋白信号通路抑制肺癌细胞增殖、迁移、侵袭并促进细胞凋亡OA

Objective:This study aims to observe the effects of Solanine on the malignant biological behavior of lung cancer cells and to explore possible mechanisms of action.Methods:The A549 and H-1299 lung cancer cell lines were exposed to varying concentrations of Solanine to identify the optimal dosage.Cell viability,proliferation,migra-tion,and invasion were assessed using the cell counting kit 8(CCK-8)assay,colony formation assay,5-ethynyl-2'-de-oxyuridine nucleoside assay,and Trans well assay,respectively.Apoptosis and nuclear morphology of apoptotic cells were evaluated through flow cytometry and Hoechst 33342 staining.Additionally,quantitative real-time PCR(qRT-PCR)and Western blot analysis were employed to examine the effects of Solanine on apoptosis-related proteins and the Wnt/β-catenin signaling pathway.Results:The CCK-8 assay results indicated that lobelia exerted a concentration-dependent inhibitory effect on the viability of lung cancer cells,with the most pronounced effect observed at a concen-tration of 25 μmol/L(P＜0.05).Colony formation and Transwell assays further demonstrated that lobelia effectively suppressed the proliferation and invasion of lung cancer cells(P＜0.05).Flow cytometry and Hoechst 33342 staining revealed that Solanine increased apoptosis rates and induced characteristic apoptotic morphological changes,such as chromatin condensation and nuclear fragmentation(P＜0.05,P＜0.01).Western blot analysis showed an upregula-tion of Cleaved caspase-3,Cleaved caspase-9,and Bcl-2 related X protein(Bax)protein levels,alongside a downregu-lation of B-cell lymphoma-2(Bcl-2)protein levels in lung cancer cells(all P＜0.05).Additionally,qRT-PCR and Western blot analyses indicated that Solanine significantly down-regulated the expression of β-catenin,a key molecule of the Wnt/β-catenin signaling pathway,and its downstream target genes,cellular Myc(c-Myc)and Cyclin D1,at the mRNA and protein levels in lung cancer cells.Simultaneously reduced the expression of glycogen synthase kinase-3 beta(GSK-3β)gene and protein(all P＜0.05).Notably,the inhibitory effects of Solanine on cell viability and inva-sion were partially reversed by LiCL treatment,an activator of the Wnt/β-catenin signaling pathway(P＜0.05,P＜0.01).Conclusion:Solanine may inhibit the malignant biological behavior of lung cancer cells via modulating the Wnt/β-catenin signaling pathway.These results offer novel insights and directions for the development of new and effective anti-lung cancer therapeutics.