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Background: 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.
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 on a prostate cancer xenograft model using 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.Â Â
Results: A combination therapy of 1 ÂµM Desmopressin with 100nM Docetaxel resulted in dramatic inhibition of proliferation of DU145 cells 72 hours post treatment compared to either agent along (p < 0.05). Wound healing assay revealed inhibition of cellular migration as well (p<0.05). The use of a xenograft mouse model followed by treatment with 5 mg/kg Docetaxel intraperitoneally with concomitant 2 Âµg/ml/kg Desmopressin administered intravenously 30 minutes before administering chemotherapy and 24 hours after, resulted in a significant decrease in tumor volume (P<0.05), while not impacting body weight.
Conclusions: Desmopressin significantly 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.
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