Inhibition of Bruton’s tyrosine Kinase suppresses cancer stemness and promotes carboplatin-induced cytotoxicity against bladder cancer cells

Yueh Pan, Ya Hsu Chiu, Shao Chih Chiu, Der Yang Cho, Liang Ming Lee, Yu Ching Wen, Jacqueline Whang-Peng, Chi Hao Hsiao, Ping Hsiao Shih

研究成果: 雜誌貢獻文章同行評審

5 引文 斯高帕斯(Scopus)

摘要

Background/aim: Bruton’s tyrosine kinase (BTK) has been discovered to serve a critical role in the survival and infiltration of B-cell lymphoma. Recently, it was reported that BTK inhibitors exerted potential beneficial effects against numerous types of solid tumor, including glioblastoma multiforme and breast cancer; however, whether BTK is crucial for the progression of bladder cancer (BLCA) remains unclear. The present study investigated the in vitro function of BTK in stemness properties of BLCA cells. Furthermore, the therapeutic effects of a standard chemotherapeutic drug, carboplatin in combination with the BTK inhibitor, ibrutinib were also investigated. Materials and Methods: The association between BTK and BLCA progression was evaluated using free databases. The in vitro stemness and metastatic properties of BLCA cells were also investigated. Finally, the cytotoxicity of carboplatin in combination with ibrutinib was determined. Results: The meta-survival analysis of the association between BTK and BLCA progression revealed that the expression levels of BTK were associated with a higher risk of BLCA progression. The CD133+-side population of BLCA cells formed spheroids when cultured in serum-free conditioned medium. In addition, expression levels of BTK and activated mTOR signaling in side population cells was up-regulated compared with the parental BLCA cells. Furthermore, the transfection of short hairpin RNA targeting BTK into BLCA cells markedly reduced cell migratory ability. More importantly, in advanced BLCA cells, which were more resistant to carboplatin, it was discovered that the cell viability was significantly reduced in the presence of ibrutinib (p<0.05). Conclusion: The findings of the present study suggested that BTK may have a critical role in the progression of BLCA; however, the underlying mechanisms and potential therapeutic strategies involved require further investigations.

原文英語
頁(從 - 到)6093-6099
頁數7
期刊Anticancer Research
40
發行號11
DOIs
出版狀態已發佈 - 十一月 2020

ASJC Scopus subject areas

  • 腫瘤科
  • 癌症研究

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