31 July 2015 : Laboratory Research
Specific Inhibition of β-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces ApoptosisJinshui HeCD, Yiqun HuangCDE, Jianmin WengEF, Liyun XiaoFG, Kaizhi WengCF, Xudong MaABC
Med Sci Monit 2015; 21:2218-2224
BACKGROUND: The canonical Wnt signaling pathway has been considered as a potent oncogenic signaling in the initiation and progression of hematological malignancies. As a key regulator of the Wnt signaling pathway, the role of β-catenin in mantle cell lymphoma (MCL) pathogenesis and progression was investigated in this study.
MATERIAL AND METHODS: A total of 30 MCL samples were collected from patients and were examined for the expression of β-catenin and p-GSK3β using immunohistochemical (IHC) staining. Further in vitro studies employed MTT and Western blot assays detecting proliferation and apoptosis-related proteins in MCL cell line Jeko-1, which were transfected with β-catenin shRNA or specific inhibitor XAV939.
RESULTS: Expression of β-catenin and phosphorylated glycogen synthase kinase-3 beta (p-GSK3β) in MCL was significantly higher than those in controlled samples. In vitro studies indicated that β-catenin knockdown significantly inhibited cell proliferation and induced apoptosis in Jeko-1 cells. Furthermore, XAV939 induced apoptosis and growth arrest in Jeko-1 cells. Both inhibitory agents increased Bax and caspase 3 proteins, and decreased Bcl-2, c-Myc, and Cyclin D1 proteins.
CONCLUSIONS: The specific inhibition of β-catenin induces apoptosis and growth arrest, making it a potential therapeutic target against MCL.
Keywords: Cell Proliferation - drug effects, Heterocyclic Compounds, 3-Ring - pharmacology, Lymphoma, Mantle-Cell - pathology, beta Catenin - antagonists & inhibitors
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