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

Anticancer Res. 2016 Feb;36(2):633-41.

Abstract

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.

Conclusion: Kinase inhibition may be an appropriate strategy for the treatment of prostate cancer.

Keywords: Prostate cancer; androgen receptor; kinase inhibitors; resistance; therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgen Antagonists / pharmacology*
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Drug Resistance, Neoplasm / drug effects*
  • Humans
  • Male
  • Mutation / genetics
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / enzymology
  • Prostatic Neoplasms / pathology
  • Protein Kinase Inhibitors / pharmacology*
  • Protein Kinases / chemistry*
  • Receptors, Androgen / genetics
  • Receptors, Androgen / metabolism*
  • Tumor Cells, Cultured

Substances

  • AR protein, human
  • Androgen Antagonists
  • Protein Kinase Inhibitors
  • Receptors, Androgen
  • Protein Kinases