Login to Access Video or Poster Abstract: MP83-17
Sources of Funding: none

Introduction

This study was designed to assess the efficacy of the combination of Desmopressin and Docetaxel for prostate cancer. Desmopressin has been demonstrated to inhibit tumor progression and metastasis in in vitro and in vivo models of breast cancer. Docetaxel, an anti-mitotic chemotherapeutic agent, is widely used for the treatment of castration resistant prostate cancer. However, it is associated with adverse effects and eventual drug resistance. This is the first report on the effect of combining Desmopressin and Docetaxel in prostate cancer, both in vitro and in vivo. _x000D_

Methods

An established castrate resistant prostate cancer cell line DU145 was used. Cellular proliferation was determined using the MTS assay. The migratory inhibition potential of Desmopressin alone and in combination with Docetaxel was accessed using the wound healing assay. In vivo evaluation was performed by using a prostate cancer xenograft model of athymic nude mouse. Treatment was administered bi- weekly and tumor volume were measured throughout the treatment period. Eventually, after a six-week treatment period, tumors were excised and measured. _x000D_

Results

combination therapy of 1 μM Desmopressin with 100nM Docetaxel resulted in inhibition of proliferation of DU145 cells 72 hours post treatment compared to either agent along (Figure 1). Wound healing assay revealed inhibition of cellular migration as well (p<0.05). In the xenograft mouse model, treatment with 5 mg/kg Docetaxel intraperitoneally with concomitant 2 μg/ml/kg Desmopressin administered intravenously 30 minutes before administering chemotherapy and 24 hours later resulted in a significant decrease in tumor volume compared to Docetaxel alone, while not impacting body weight.

Conclusions

Desmopressin enhanced the anti-proliferative and inhibiting the migratory potential of Docetaxel. Combination treatment had no additional effect on mice weight or mortality. These studies could enhance the efficacy of Docetaxel- based chemotherapy treatment for castrate resistant prostate cancer.

Funding

none