Ganoderma lucidum Exerts an Anticancer Effect on Human Osteosarcoma Cells via Suppressing the Wnt/β-Catenin Signaling Pathway

Background: Current treatment of osteosarcoma is limited in part by side effects and low tolerability, problems generally avoided with traditional Chinese medicine. Ganoderma lucidum, a traditional Chinese medicine with antitumor effects, offers a potential alternative, but little is known about its molecular mechanisms in osteosarcoma cells. Objective: To investigate the effect of G lucidum on osteosarcoma cells and its mechanism. Methods: Osteosarcoma MG63 and U2-OS cells were treated with G lucidum, followed by assays for cell proliferation (Cell Counting Kit-8), colony formation, and apoptosis (Alexa Fluor 647-Annexin V/propidium iodide, flow cytometry). Migration and invasion of cells were assessed by wound healing and Transwell invasion assays, and the effect of G lucidum on Wnt/β-catenin signal transduction was studied by real-time quantitative polymerase chain reaction, western blot, and dual-luciferase assay. Results: G lucidum inhibited the proliferation, migration, and invasion, and induced apoptosis of human osteosarcoma MG63 and U2-OS cells. Dual-luciferase assay showed that G lucidum suppressed the transcriptional activity of T-cell factor/lymphocyte enhancer factor in the Wnt/β-catenin signaling pathway. Moreover, G lucidum blocked Wnt/β-catenin signaling by inhibiting the Wnt co-receptor LRP5 and Wnt-related target genes, such as β-catenin, cyclin D1, C-Myc, MMP-2, and MMP-9. At the same time, when Wnt/β-catenin was inhibited, the expression of E-cadherin was upregulated. Conclusions: Our results suggest that G lucidum broadly suppresses osteosarcoma cell growth by inhibiting Wnt/β-catenin signaling.