2016 Fiscal Year Final Research Report
Zoledronic acid sensitizes castration resistant prostate cancer cells to radiotherapy and chemotherapy by downregulating STAT1
| Project/Area Number |
15K20072
|
|---|
| Research Category |
Grant-in-Aid for Young Scientists (B)
|
| Allocation Type | Multi-year Fund |
|---|
| Research Field |
Urology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2015-04-01 – 2017-03-31
|
| Keywords | 前立腺癌 / 放射線治療 / 化学療法 |
|---|
| Outline of Final Research Achievements |
Androgen independent cell lines (PC3, DU145) expressed STAT1 higher than androgen dependent LNCaP cells. STAT1 was gradually upregulated in LNCaP as it acquired androgen independency by continuous androgen ablation. Zoledronic acid decreased STAT1 at protein level by proteasome-mediated degradation and sensitized PC3 and DU145 to both radiotherapy and chemotherapy. Functional siRNA knockdown of STAT1 resulted in the sensitization of DU145 to radiotherapy and chemotherapy. Forced expression of STAT1 in LNCaP rendered it resistant to those therapies. In conclusion, we demonstrated that zoledronic acid sensitizes castration-resistant prostate cancer cells to radiotherapy and chemotherapy by downregulating STAT1. Zoledronic acid decreased STAT1 at protein level by proteasome-mediated degradation. These results may be useful in the treatment of patients with castration-resistant prostate cancer cells.
|
| Free Research Field |
泌尿器癌
|
