IRL-1620, a tumor selective vasodilator, augments the uptake and efficacy of chemotherapeutic agents in prostate tumor rats

BACKGROUND. IRL-1620, a potent endothelin B receptor agonist, enhanced the efficacy of paclitaxel in a breast tumor model, but its effect in prostate cancer is not known. The present study was conducted to evaluate the effect of IRL-1620 on tumor perfusion, uptake of [¹⁴C]-doxorubicin in the tumor and efficacy of doxorubicin (DOX), and 5-flurouracil (5-FU) in a rat prostate tumor model. METHODS. JHU-4 (Mat-Lu) cells inoculated prostate tumor model in Copenhagen rats was used for the study. RESULTS. Administration of IRL-1620 (3 nmol/kg, i.v) significantly increased (102.8%) prostate tumor perfusion and tumor uptake of [¹⁴C]-doxorubicin (115%) compared to vehicle treated rats. Results of the efficacy study demonstrate that IRL-1620 administration 15 min prior to DOX (5 mg/kg) or 5-FU (50 mg/kg) on every third day for a total of four doses significantly reduced tumor volume compared to vehicle treated rats. CONCLUSIONS. IRL-1620 significantly enhanced the uptake and efficacy of anticancer agents in prostate cancer.