Cholecystokinin stimulates growth of human pancreatic adenocarcinoma SW-1990.
The effect of a synthetic analogue of CCK (Thr4,Nle7CCK-9) on growth of SW-1990 human pancreatic cancer was examined in two experimental models. Nude mice bearing SW-1990 pancreatic cancer xenografts were injected with CCK (5, 15, or 25 micrograms/kg) or vehicle twice daily for 20 days. Animals were then sacrificed and tumor volume, weight, protein, and deoxyribonucleic acid (DNA) content were evaluated. SW-1990 cells were grown in vitro and the effects of CCK, secretin, vasoactive intestinal peptide (VIP), and proglumide (a CCK-receptor antagonist) on cell number and DNA synthesis were determined. The highest dose of CCK, 25 micrograms/kg, significantly increased tumor weight, protein content, and DNA content (P less than 0.005). In vitro, CCK caused significant increases in cell counts of up to 47% at six days and 66% at 12 days compared to control. Graded concentrations of CCK had a biphasic effect on DNA synthesis with significant increases of up to 65% (P less than 0.005). CCK-induced cell proliferation was inhibited by proglumide. Secretin slightly increased cancer cell growth, although not as potently as CCK, VIP or secretin in combination with CCK did not show potentiation. These results indicate that growth of some human pancreatic cancers may be influenced by gastrointestinal peptides, of which CCK is the most potent.
Smith
J P
JP
Department of Medicine, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Solomon
T E
TE
Bagheri
S
S
Kramer
S
S
D000230:Adenocarcinoma / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology*; D004273:DNA, Neoplasm / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009929:Organ Size; D010179:Pancreas / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000473:pathology; D011377:Proglumide / Q000494:pharmacology; D012633:Secretin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology
D004273:DNA, Neoplasm; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D002766:Cholecystokinin; D011377:Proglumide