R Romani1, L G Howes, D L Morris. 1. University of New South Wales, Department of Surgery, St George Hospital, Kogarah, Australia.
Abstract
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%. CONCLUSION: 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.
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 humancolon 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%. CONCLUSION: 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.