Dose dependent in vivo inhibition of human colorectal cancer (LoVo) by the gastrin receptor antagonist, CI-988.
1. The dose-response relationship of a new, potent and selective cholecystokinin B receptor antagonist, CI-988, on the growth of LoVo, a human colon cancer cell line, was studied in vivo. 2. We have previously shown the growth of LoVo to be inhibited both in vitro and in vivo by CI-988. 3. LoVo was grown for 10 days in nude mice that were then treated with CI-988 at 1, 5, 10, 25 and 50 mg/kg per day orally for 20 days. 4. CI-988 significantly inhibited the growth of xenografts at all concentrations except the highest concentration of 50 mg/kg per day (P < 0.00001; ANOVA). The largest inhibitory activity was caused by the 10 mg/kg per day dose, causing a 47% inhibition at day 29 (P = 0.00003: Newman-Keul's test). 5. CI-988 may be of use in inhibiting the growth of colorectal cancer.
Romani
R
R
University Department of Surgery, University of New South Wales, Kogarah, Australia.
Howes
L G
LG
Morris
D L
DL
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation / Q000473:pathology; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D007211:Indoles; D011949:Receptors, Cholecystokinin; C065599:PD 134308; D008536:Meglumine