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.
Keywords:
Bruton’s tyrosine kinase (Btk); cancer stem cell (CSC); cisplatin; ibrutinib; ovarian cancer; spheroids.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenine / analogs & derivatives
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Adult
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Agammaglobulinaemia Tyrosine Kinase
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Antineoplastic Agents / therapeutic use*
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Cisplatin / therapeutic use
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Drug Resistance, Neoplasm
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Drug Therapy, Combination
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Female
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Humans
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Janus Kinase 2 / metabolism
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Middle Aged
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Neoplastic Stem Cells / drug effects*
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Ovarian Neoplasms / drug therapy*
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Ovarian Neoplasms / metabolism
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Ovarian Neoplasms / mortality
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Piperidines
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Protein-Tyrosine Kinases / antagonists & inhibitors*
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Pyrazoles / therapeutic use*
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Pyrimidines / therapeutic use*
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STAT3 Transcription Factor / metabolism
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Young Adult
Substances
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Antineoplastic Agents
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Piperidines
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Pyrazoles
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Pyrimidines
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STAT3 Transcription Factor
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STAT3 protein, human
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ibrutinib
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Protein-Tyrosine Kinases
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Agammaglobulinaemia Tyrosine Kinase
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BTK protein, human
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JAK2 protein, human
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Janus Kinase 2
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Adenine
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Cisplatin