Abstract：
:Bruton's tyrosine kinase (Btk) is a member of the Tec-family non-receptor tyrosine kinases family. It has previously been reported to be expressed in B cells and has an important role in B-cell malignancies. While the roles of Btk in the pathogenesis of certain B-cell malignancies are well established, the functions of Btk in gastric carcinoma have never been investigated. Herein, we found that Btk is over-expressed in gastric carcinoma tissues and gastric cancer cells. Knockdown of Btk expression selectively inhibits the growth of gastric cancer cells, but not that of the normal gastric mucosa epithelial cell, which express very little Btk. Inhibition of Btk by its inhibitor ibrutinib has an additive inhibitory effect on gastric cancer cell growth. Treatment of gastric cancer cells, but not immortalized breast epithelial cells with ibrutinib results in effective cell killing, accompanied by the attenuation of Btk signals. Ibrutinib also induces apoptosis in gastric carcinoma cells as well as is a chemo-sensitizer for docetaxel (DTX), a standard of care for gastric carcinoma patients. Finally, ibrutinib markedly reduces tumor growth and increases tumor cell apoptosis in the tumors formed in mice inoculated with the gastric carcinoma cells. Given these promising preclinical results for ibrutinib in gastric carcinoma, a strategy combining Btk inhibitor warrants attention in gastric cancer.
journal_name
Am J Transl Resjournal_title
American journal of translational researchauthors
Wang JD,Chen XY,Ji KW,Tao Fsubject
Has Abstractpub_date
2016-07-15 00:00:00pages
3003-12issue
7issn
1943-8141journal_volume
8pub_type
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journal_title：American journal of translational research
pub_type： 杂志文章
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更新日期：2020-07-15 00:00:00
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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journal_title：American journal of translational research
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