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

布鲁顿酪氨酸激酶 (Btk) 抑制剂伊布替尼可抑制卵巢癌的干细胞样特征

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

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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