Specific Inhibition of β-Catenin in Jeko-1 Mantle Cell Lymphoma Cell Line Decreases Proliferation and Induces Apoptosis.

Abstract:

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.

journal_name

Med Sci Monit

authors

He J,Huang Y,Weng J,Xiao L,Weng K,Ma X

doi

10.12659/MSM.893514

subject

Has Abstract

pub_date

2015-07-31 00:00:00

pages

2218-24

eissn

1234-1010

issn

1643-3750

pii

893514

journal_volume

21

pub_type

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