Role of Wnt/β-catenin pathway in inducing autophagy and apoptosis in multiple myeloma cells

beta-catenin is the downstream effector of the Wnt signaling pathway, which regulates cell proliferation and differentiation. Activation of the Wnt/beta-catenin signaling pathway has been shown to positively correlate with prognosis in several types of malignancies. The present study aimed to determine the role of beta-catenin in multiple myeloma (MM) cells using lentiviruses expressing small interfering RNA (siRNA). The expression of beta-catenin in the MM cell line RPMI-8826 was evaluated following beta-catenin knockdown by the siRNA. Subsequently, the activation of autophagy in MM cells was assessed by transmission electron microscopy and western blot analyses. Cell apoptosis and the expression of apoptosis-related proteins following beta-catenin silencing was investigated by flow cytometry and western blotting, respectively. A significant decrease in beta-catenin expression was observed in the MM cell line expressing beta-catenin-specific siRNA. Activation of autophagy was induced by beta-catenin silencing, as evidenced by increases in the number of autophagic vacuoles and the expression of the autophagy-related proteins microtubule-associated protein 1 light chain 3 and Beclin-1. Furthermore, the expression of 5'-adenosine monophosphate-activated protein kinase was increased, and that of mechanistic target of rapamycin was decreased, following beta-catenin silencing. In addition, there was an increase in the rate of apoptosis of MM cells following beta-catenin silencing, accompanied by increased protein expression of phosphorylated p53, active caspase-3 and B-cell lymphoma (Bcl)-2-associated X protein, and decreased protein expression of Bcl-2. The results of the present study suggested that beta-catenin silencing induced autophagy and apoptosis in MM cells. To the best of our knowledge, this is the first study to demonstrate that a beta-catenin deficiency induces autophagy in MM cells. These findings suggested that inhibition of beta-catenin could be a potential therapeutic target for patients with MM.