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%.

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.