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

Su,Nan; Wang,Pingping; Li,Yan

doi:10.3892/ol.2016.5289

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

Authors:
- Nan Su
- Pingping Wang
- Yan Li
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Affiliations: Department of Hematology, First Affiliation Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: October 18, 2016 https://doi.org/10.3892/ol.2016.5289
Pages: 4623-4629
Copyright: © Su et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

β-catenin is the downstream effector of the Wnt signaling pathway, which regulates cell proliferation and differentiation. Activation of the Wnt/β‑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 β‑catenin in multiple myeloma (MM) cells using lentiviruses expressing small interfering RNA (siRNA). The expression of β‑catenin in the MM cell line RPMI‑8826 was evaluated following β‑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 β‑catenin silencing was investigated by flow cytometry and western blotting, respectively. A significant decrease in β‑catenin expression was observed in the MM cell line expressing β‑catenin‑specific siRNA. Activation of autophagy was induced by β‑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 β‑catenin silencing. In addition, there was an increase in the rate of apoptosis of MM cells following β‑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 β‑catenin silencing induced autophagy and apoptosis in MM cells. To the best of our knowledge, this is the first study to demonstrate that a β‑catenin deficiency induces autophagy in MM cells. These findings suggested that inhibition of β‑catenin could be a potential therapeutic target for patients with MM.

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