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

AbstractBACKGROUND:
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.
AuthorsN V Rajeshkumar, George Matwyshyn, Anil Gulati
JournalThe Prostate (Prostate) Vol. 67 Issue 7 Pg. 701-13 (May 15 2007) ISSN: 0270-4137 [Print] United States
PMID17342753 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Copyright(c) 2007 Wiley-Liss, Inc.
Chemical References
  • Antibiotics, Antineoplastic
  • Antimetabolites, Antineoplastic
  • Antineoplastic Agents
  • Endothelins
  • Peptide Fragments
  • Receptor, Endothelin B
  • Vasodilator Agents
  • IRL 1620
  • Doxorubicin
  • Fluorouracil
Topics
  • Animals
  • Antibiotics, Antineoplastic (pharmacokinetics, therapeutic use)
  • Antimetabolites, Antineoplastic (pharmacokinetics, therapeutic use)
  • Antineoplastic Agents (pharmacokinetics, therapeutic use)
  • Biological Transport (drug effects)
  • Body Weight (drug effects)
  • Doxorubicin (pharmacokinetics, therapeutic use)
  • Endothelins (pharmacology)
  • Fluorouracil (pharmacokinetics, therapeutic use)
  • Male
  • Peptide Fragments (pharmacology)
  • Prostatic Neoplasms (blood supply, drug therapy)
  • Rats
  • Rats, Inbred Strains
  • Receptor, Endothelin B (agonists)
  • Vasodilation (drug effects)
  • Vasodilator Agents (pharmacology)

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