Abstract Casticin is a polymethoxyflavone compound with anti-tumor effect, but whether it can antagonize osteosarcoma (OS) and its possible mechanism remains to be further explored. The OS cells 143B and MG63 were treated with Casticin. The drug-resistant cells 143B/DOXR and MG63/DOXR were constructed. The drug resistance markers were detected to screen suitable drug-resistant cells. 143B/DOXR cells were treated with Casticin, DOX and Casticin+DOX, respectively. Western blot and immunofluorescence were detected β-catenin/STAT3 pathway. The stem cell-like properties of 143B cells were evaluated by stem cell sphere formation assay and Western blot. Finally, the inhibitory effects of Casticin on OS growth and DOX resistance were verified by nude mouse xenograft experiments. Casticin significantly attenuated the malignant phenotype of OS cells, and reduced the sphere-forming ability of stem cells. Both 143B/DOXR and MG63/DOXR cells showed significant resistance to DOX, and the drug resistance of 143B/DOXR cells was better. Casticin and DOX can significantly inhibit the malignant progression of 143B/DOXR cells, and the combined intervention of Casticin+DOX has a stronger inhibitory effect. Casticin significantly lessened β-catenin and p-STAT3/STAT3 protein levels, while overexpression of β-catenin markedly promoted cell malignant progression and increased stem cell sphere-forming ability and marker levels. In addition, Casticin also inhibited OS growth and metastasis, promoted cell apoptosis, and inhibited stem cell markers in 143B cells and drug resistance markers in 143B/DOXR cells. Casticin can inhibit the occurrence, stem cell-like properties and DOX resistance of OS through inhibiting β-catenin/STAT3 pathway, and has the potential of anti-tumor and reversing chemotherapeutic drug resistance.
Ding et al. (Mon,) studied this question.