BHX Inhibits the Wnt Signaling Pathway by Suppressing β-catenin Transcription in the Nucleus

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作者
Fengxia Ding
Meisa Wang
Yibo Du
Shuangshuang Du
Zhongling Zhu
Zhao Yan
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[1] Tianjin Medical University Cancer Institute and Hospital,Department of Clinical Pharmacology
[2] National Clinical Research Center for Cancer,undefined
[3] Key Laboratory of Cancer Prevention and Therapy,undefined
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BHX (N-(4-hydroxybenzyl)-1,3,4-triphenyl-4,5-dihydro-1H-pyrazole-5-carboxamide), a Wnt signaling pathway inhibitor, effectively inhibits tumor cell growth, but the underlying mechanism is unclear. Thus, we aim to investigate the effects and associated mechanism of BHX action on A549 and MCF-7 cell lines. In our study, MTT(3-[4,5-dimethyl-2-thiazolyl]-2,5-diphenyl-2H-tetrazolium bromide) and xenograft model assay indicated that cell growth was inhibited by BHX at a range of concentrations in vitro and in vivo. The expression of β-catenin and Wnt signaling pathway downstream target genes were decreased evidently under BHX treatment. Flow cytometry also revealed that BHX treatment significantly induced G1 arrest. Further analysis showed that BHX lowered the transcriptional level of β-catenin. In conclusion, BHX inhibited the nuclear synthesis of β-catenin, thereby suppressing the Wnt signaling pathway and further inhibiting tumor growth and proliferation.
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