Cholecystokinin inhibition of tumor growth and gastrin-stimulated cyclic adenosine 3':5'-monophosphate metabolism in human gastric carcinoma in nude mice.
This study deals with the effect of four types of COOH-terminal cholecystokinin (CCK) fragments on the growth of xenotransplantable human gastric cancer (SC-6-JCK, a poorly differentiated adenocarcinoma) whose growth has been promoted by pentagastrin. The growth of the tumor was inhibited using daily s.c. injections of CCK-octapeptide (CCK-8) and glutaryl-CCK-8 at a dose of 500 micrograms/kg body weight. After 30 days of treatment with CCK-8 or glutaryl-CCK-8, a significant decrease was observed in the tumor weight (P less than 0.05) and the tumor size P less than 0.01) in comparison with those of the control. But treatment with CCK-12 and pyroglutamyl-CCK-8 did not produce inhibition of tumor growth. Furthermore the correlation between the effect of CCK-8 on the normal rise in tumor cyclic adenosine 3':5'-monophosphate (cAMP) levels caused by pentagastrin injection and tumor growth was studied. The increase of cAMP by a single i.p. injection of pentagastrin at a dose of 20 micrograms/mouse was significantly inhibited by pretreatment with CCK-8 at concentrations equimolar to pentagastrin (P less than 0.05), while cAMP in the tumor was slightly elevated by a single i.p. injection of CCK-8 alone. Also in the in vitro study, CCK-8 inhibited the increase of cAMP and the activation of cAMP-dependent protein kinase which was stimulated by pentagastrin. These results suggest that proliferation of gastrin-dependent human gastric cancers may be suppressed by CCK in competition with gastrin.
D000230:Adenocarcinoma / Q000188:drug therapy*; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D010418:Pentagastrin / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism; D012844:Sincalide / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy*
D002766:Cholecystokinin; D000242:Cyclic AMP; D011494:Protein Kinases; D010418:Pentagastrin; D012844:Sincalide