Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer

Muhammad Ary Zucha; Alexander T.H. Wu; Wei-Hwa Lee; Liang-Shun Wang; Wan-Wan Lin; Chiou-Chung Yuan; Chi-Tai Yeh

doi:10.18632/oncotarget.3658

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Research Papers:

Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer

Muhammad Ary Zucha, Alexander T.H. Wu, Wei-Hwa Lee, Liang-Shun Wang, Wan-Wan Lin, Chiou-Chung Yuan and Chi-Tai Yeh _

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Oncotarget. 2015; 6:13255-13268. https://doi.org/10.18632/oncotarget.3658

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Abstract

Muhammad Ary Zucha1,2, Alexander T.H. Wu3,4, Wei-Hwa Lee5, Liang-Shun Wang6, Wan-Wan Lin1, Chiou-Chung Yuan7, Chi-Tai Yeh6,8

1 Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan

2 Department of Obstetrics and Gynecology, Gadjah Mada University-Sardjito Central Hospital, Yogyakarta, Indonesia

3 Graduate Institute of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

4 Translational Research Laboratory, Cancer Center, Taipei Medical University Hospital, Taipei, Taiwan

5 Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

6 Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

7 Obstetrics and Gynecology Department, Shuang-Ho Hospital, Taipei, Taiwan

8 Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan

Correspondence to:

Chi-Tai Yeh, email:

Chiou-Chung Yuan, email:

Keywords: ovarian cancer, cancer stem cell (CSC), spheroids, ibrutinib, Bruton’s tyrosine kinase (Btk), cisplatin

Received: December 14, 2014 Accepted: February 28, 2015 Published: March 26, 2015

Abstract

According to a Prognoscan database, upregulation of Bruton’s tyrosine kinase (Btk) is associated with low overall survival in ovarian cancer patients. We found that spheroids-forming ovarian cancer cell, which highly expressed cancer stem-like cell (CSC) markers and Btk, were cisplatin resistant. We next treated CSCs and non-CSCs by a combination of ibrutinib and cisplatin. We found that chemoresistance was dependent on Btk and JAK2/STAT3, which maintained CSC by inducing Sox-2 and prosurvival genes. We suggest that addition of ibrutinib to cisplatin may improve treatment outcome in ovarian cancer.

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Research Papers:

Bruton’s tyrosine kinase (Btk) inhibitor ibrutinib suppresses stem-like traits in ovarian cancer

Abstract