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