Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer.

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Ramachandran K,Speer C,Nathanson L,Claros M,Singal R

subject

Has Abstract

pub_date

2016-01-01 00:00:00

pages

161-8

issue

1

eissn

0250-7005

issn

1791-7530

pii

36/1/161

journal_volume

36

pub_type

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