Growth inhibition of human pancreatic cancer cells by cholecystokinin receptor antagonist in tissue culture and in nude mice.
The Human pancreatic carcinoma cell line KP-1N and its clone KP-1NL which has a high rate of liver metastasis were established. Ki-ras DNA point mutation on the codon 12 was found. The growth of KP-1N was stimulated by a physiological range of concentration (10(-11)-10(-10) M) of cholecystokinin and the increase was inhibited by the addition of a cholecystokinin receptor antagonist (CR 1505). Daily injections of CR 1505 (35 mg/kg) diminished the number of tumor colonies in the liver that were formed after an intrasplenic injection of the highly liver metastatic KP-1NL cells. These results suggest that cholecystokinin antagonists may be useful as growth inhibitors for some pancreatic cancer.
Funakoshi
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Division of Gastroenterology, National Kyushu Cancer Center, Fukuoka, Japan.
Kono
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D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000818:Animals; D002108:Ceruletide / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008113:Liver Neoplasms / Q000188:drug therapy / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
C053737:loxiglumide; D002108:Ceruletide; D002766:Cholecystokinin; D011377:Proglumide