Multiple myeloma (MM) is thrombogenic as a consequence of multiple hemostatic effects. Overexpression of beta-catenin has been observed in several types of malignant tumors, including MM. However, the relationship between beta-catenin expression and MM remains unclear. In the present study, RNA interference was used to inhibit beta-catenin expression in RPMI8226 cells. RT-PCR and Western blotting analyses showed that beta-catenin mRNA and protein expression were markedly down-regulated by CTNNB1 shRNA. Western blotting showed that the protein levels of cyclin D1 and glutamine synthetase were downregulated and supported the transcriptional regulatory function of beta-catenin. The MTT assay showed that CTNNB1 shRNA could have significant inhibitory effects on the proliferation of RPMI8226 cells. The TOP-flash reporter assay demonstrated significant downregulation after CTNNB1 shRNA transfection in RPMI8226 cells. Flow cytometric analyses also showed significantly profound apoptosis in CTNNB1 shRNA cells. We found CTNNB1 silence led to growth inhibition of MM growth in vivo. Immunohistochemical analyses showed that c-myc and beta-catenin were reduced in CTNNB1 shRNA tumor tissues, but that expression of cleaved caspase-3 was increased. These results show that beta-catenin could be a new therapeutic agent that targets the biology of MM cells. (C) 2012 Elsevier Inc. All rights reserved.