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 language | English (US) |
|---|---|
| Pages (from-to) | 161-168 |
| Number of pages | 8 |
| Journal | Anticancer Research |
| Volume | 36 |
| Issue number | 1 |
| State | Published - Jan 1 2016 |
Keywords
- DNA methylation
- drug resistance
- Epigenetics
- prostate cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research