Sensitivity Profiles of Human Prostate Cancer Cell Lines to an 80 Kinase Inhibitor Panel

BACKGROUND - Taxanes and anti-androgen therapies are routinely used for the treatment of metastatic prostate cancer, however the majority of patients eventually develop resistance.

MATERIALS AND METHODS - Eighty kinase inhibitors were screened regarding their ability to inhibit cell viability in CWR22, 22Rv1, PC-3 and DU145 prostate cancer cells using automated toxicity assays.

Four kinase inhibitors were selected for further investigation.

RESULTS - No significant difference in sensitivity patterns was found between the androgen receptor wild-type CWR22 and its androgen receptor mutant variant 22Rv1, indicating that androgen receptor mutation did not impact on kinase inhibitor sensitivity in this model. Metastatic PC-3 and DU145 prostate cancer cell lines were less sensitive to kinase inhibitors than the non-metastatic CWR22 and 22Rv1. All four cell lines responded to GSK-3 inhibitor BIO, and MEK inhibitor PD198306. DU145 cells were resistant to p75NTR/TrkA and CHK4 inhibitors, RO-082750 and Ryuvidine.

CONCLUSIONS - Kinase inhibition may be an appropriate strategy for the treatment of prostate cancer.

Anticancer research. 2016 Feb [Epub]

Amy J Burke, Husnain Ali, Enda O'Connell, Francis J Sullivan, Sharon A Glynn

Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland. , Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland. , Screening Core, National Centre for Biomedical Engineering Science, National University of Ireland Galway, Galway, Ireland. , Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland HRB Clinical Research Facilities Galway, National University of Ireland Galway, Galway, Ireland. , Prostate Cancer Institute, National University of Ireland Galway, Galway, Ireland Discipline of Pathology, Lambe Institute for Translational Research, School of Medicine, National University of Ireland Galway, Galway, Ireland Apoptosis Research Centre, National University of Ireland Galway, Galway, Ireland 

PubMed

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