Gastrin receptor antagonist CI-988 inhibits growth of human colon cancer in vivo and in vitro.
BACKGROUND
Whilst gastrin has been found to be trophic for some colorectal cancer cell lines, and gastrin receptor antagonists are able to block this phenomenon, their potency has been modest.


METHODS
The effect of a new, potent and selective CCK B receptor antagonist, CI-988 on the growth of LoVo, a human colon cancer cell line both in vitro and in vivo was instigated.


RESULTS
Basal growth of LoVo in vitro was inhibited by up to 58.93 +/- 7.30% with concentrations of CI-988 as low as 1 X 10(-11) mol/L whereas the addition of gastrin (G17) at 0.5 nmol/L had no effect. LoVo was also grown in vivo for 10 days in nude mice subsequently treated with CI-988 at 10 mg/kg per day orally for 20 days. CI-988 inhibited the growth of xenografts by 53%.


CONCLUSIONS
This was the first study in cancer with this potent gastrin receptor antagonist, CI-988. The results suggest that CI-988 may be of use in inhibiting the growth of colorectal cancer.
Romani
R
R
University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Australia.
Howes
L G
LG
Morris
D L
DL
D000284:Administration, Oral; D000704:Analysis of Variance; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D006727:Hormone Antagonists / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured / Q000187:drug effects
D006727:Hormone Antagonists; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine