Suppression of adriamycin resistance in osteosarcoma by blocking Wnt/β-catenin signal pathway.

OBJECTIVE: Wnt/β-catenin signal pathway plays a role in regulating cell proliferation and apoptosis, and is correlated with tumor onset, progression and drug resistance. B-cell lymphoma 2 (Bcl-2) is an anti-apoptotic factor inducing tumor cell drug resistance. Wnt/β-catenin signal pathway can modulate Bcl-2 expression. This study established a cell model of drug resistance using adriamycin (ADM) treatment. Wnt/β-catenin signal pathway was intervened to discuss its role in drug resistance of osteosarcoma cells.

MATERIALS AND METHODS: Expression of β-catenin and Bcl-2 was compared between U2OS and hFOB1.19 cells. ADM resistant cell line U2OS/ADM was established for comparing β-catenin and Bcl-2 expression. Cell counting kit-8 (CCK-8) assay was used to test cell proliferation, followed by flow cytometry for apoptotic rate under ADM concentrations. U2OS/ADM cells were further treated with si-β-catenin and/or β-catenin inhibitor XAV939. β-catenin and Bcl-2 expression were measured, followed by CCK-8 and flow cytometry.

RESULTS: Comparing to hFOB1.19 cells, U2OS cells had significantly elevated β-catenin and Bcl-2 expression. U2OS/ADM cells had higher β-catenin and Bcl-2 expression than U2OS, plus lower ADM sensitivity and suppressed apoptotic rate. Transfection of si-β-catenin and XAV939 suppressed β-catenin and Bcl-2 expression, and significantly enhanced ADM sensitivity and ADM-induced apoptosis.

CONCLUSIONS: Up-regulation of β-catenin plays a role in potentiating expression and downstream anti-apoptotic factor Bcl-2, and in enhancing ADM resistance of osteosarcoma U2OS cells.