Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer

Kavitha Ramachandran, Carl Speer, Lubov Nathanson, Martha Claros, Rakesh Singal

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

BACKGROUND/AIM: Cabazitaxel is an approved second-line treatment for docetaxel-refractory metastatic castration-resistant prostate cancer. However, the median time to progression on cabazitaxel is 2.8 months. We aimed to determine whether DNA methylation plays a role in cabazitaxel resistance.

MATERIALS AND METHODS: DU145 cells, resistant to docetaxel and cabaxitaxel (DU145 10DRCR), were generated from cells resistant to 10 nM docetaxel (DU145 10DR). The effect of pre-treatment with 5-azacytidine was determined with regards to cabazitaxel sensitivity. Gene expression profiling was carried-out on DU145 10DR, DU145 10DRCR and DU145 10DRCR treated with 5-azacytidine.

RESULTS: Pre-treatment of cells with 5-azacytidine resulted in enhanced sensitivity to cabazitaxel. Gene expression profiling identified a subset of genes that may be regulated by DNA methylation.

CONCLUSION: Our results indicate that DNA methylation of pro-apoptotic and cell-cycle regulatory genes may contribute to cabazitaxel resistance and pre-treatment with 5-azacytidine may restore sensitivity to cabazitaxel in prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)161-168
Number of pages8
JournalAnticancer Research
Volume36
Issue number1
StatePublished - Jan 1 2016

Keywords

  • DNA methylation
  • drug resistance
  • Epigenetics
  • prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Ramachandran, K., Speer, C., Nathanson, L., Claros, M., & Singal, R. (2016). Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer. Anticancer Research, 36(1), 161-168.