fig9

Figure 9. An overview of the Wnt/β-catenin pathway and its critical role in mediating drug resistance of sesquiterpene lactones in cancer cells. The pathway is activated when Wnt ligands bind to the FZD and LRP-5/6 receptor complex on the cell surface, triggering downstream signaling events. In the absence of Wnt ligands, β-catenin is ubiquitinated and degraded by a destruction complex consisting of Axin, APC, and GSK3β. However, when the Wnt pathway is activated, this destruction complex is inhibited, preventing β-catenin degradation. Consequently, β-catenin accumulates in the cytoplasm and translocates to the nucleus, where it activates the transcription of target genes. By activating β-catenin, the Wnt pathway enhances drug resistance through the upregulation of genes such as c-MYC, survivin, and MMP9, which play crucial roles in promoting cell proliferation. Sesquiterpene lactones counteract drug resistance by modulating β-catenin, GSK-3β, and the expression of downstream genes. FZD: Frizzled; LRP-5/6: lipoprotein receptor-related protein 5/6; APC: adenomatous polyposis coli; GSK3β: glycogen synthase kinase 3 beta.