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 [(14)C]-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 [(14)C]-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.
Rajeshkumar
N V
NV
Department of Biopharmaceutical Sciences, University of Illinois, Chicago, Illinois, USA.
Matwyshyn
George
G
Gulati
Anil
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D001692:Biological Transport / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics / Q000627:therapeutic use; D016232:Endothelins / Q000494:pharmacology*; D005472:Fluorouracil / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000098:blood supply / Q000188:drug therapy*; D051381:Rats; D011919:Rats, Inbred Strains; D044023:Receptor, Endothelin B / Q000819:agonists; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000903:Antibiotics, Antineoplastic; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D016232:Endothelins; D010446:Peptide Fragments; D044023:Receptor, Endothelin B; D014665:Vasodilator Agents; C074308:sovateltide; D004317:Doxorubicin; D005472:Fluorouracil