Potential therapeutic effect of targeting glycogen synthase kinase 3β in esophageal squamous cell carcinoma.

Scientific Reports
Dilireba BolidongToshinari Minamoto

Abstract

Esophageal squamous cell carcinoma (ESCC) is a common gastrointestinal cancer and is often refractory to current therapies. Development of efficient therapeutic strategies against ESCC presents a major challenge. Glycogen synthase kinase (GSK)3β has emerged as a multipotent therapeutic target in various diseases including cancer. Here we investigated the biology and pathological role of GSK3β in ESCC and explored the therapeutic effects of its inhibition. The expression of GSK3β and tyrosine (Y)216 phosphorylation-dependent activity was higher in human ESCC cell lines and primary tumors than untransformed esophageal squamous TYNEK-3 cells from an ESCC patient and tumor-adjacent normal esophageal mucosa. GSK3β-specific inhibitors and small interfering (si)RNA-mediated knockdown of GSK3β attenuated tumor cell survival and proliferation, while inducing apoptosis in ESCC cells and their xenograft tumors in mice. GSK3β inhibition spared TYNEK-3 cells and the vital organs of mice. The therapeutic effect of GSK3β inhibition in tumor cells was associated with G0/G1- and G2/M-phase cell cycle arrest, decreased expression of cyclin D1 and cyclin-dependent kinase (CDK)4 and increased expression of cyclin B1. These results suggest the tumo...Continue Reading

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Methods Mentioned

BETA
xenograft
Assay
ELISA
fluorescence microscopy
fluorescence-activated cell sorting
FACS
xenografts
transfection
flow cytometry

Software Mentioned

GraphPad Prism
FACSDiva
UALCAN
Keyence BZ - X700 Analyzer
GraphPad

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