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 |
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Keywords
- DNA methylation
- drug resistance
- Epigenetics
- prostate cancer
ASJC Scopus subject areas
- Oncology
- Cancer Research
Cite this
Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer. / Ramachandran, Kavitha; Speer, Carl; Nathanson, Lubov; Claros, Martha; Singal, Rakesh.
In: Anticancer Research, Vol. 36, No. 1, 01.01.2016, p. 161-168.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Role of DNA Methylation in Cabazitaxel Resistance in Prostate Cancer
AU - Ramachandran, Kavitha
AU - Speer, Carl
AU - Nathanson, Lubov
AU - Claros, Martha
AU - Singal, Rakesh
PY - 2016/1/1
Y1 - 2016/1/1
N2 - 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.
AB - 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.
KW - DNA methylation
KW - drug resistance
KW - Epigenetics
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85003046899&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85003046899&partnerID=8YFLogxK
M3 - Article
C2 - 26722040
AN - SCOPUS:85003046899
VL - 36
SP - 161
EP - 168
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 1
ER -