Effects of pancreastatin (24-49) on growth of normal pancreas and pancreatic cancer.
In the present study, the effects of pancreastatin on growth are evaluated in two human pancreatic cancer cell lines, in vivo and in vitro, and on athymic nude mouse pancreas. SW-1990 and MIA PaCa-2 pancreatic cancer cell lines were grown in serum-supplemented and serum-free medium in the presence of pancreastatin (10(-11)-10(-6) M), or cholecystokinin (CCK) (10(-11)-10(-8) M) or combinations thereof. Growth was evaluated by [3H]thymidine incorporation and cell counts. Pancreastatin significantly inhibited DNA synthesis in both cell lines, and cell counts in SW-1990 on days 3 and 5 but not 7. CCK-stimulated cell growth was inhibited in both cell lines and mouse pancreas by pancreastatin. Pancreastatin had no effect in the presence of fetal bovine serum. In the in vivo experiments, pancreastatin (15 micrograms/kg) did not affect growth of SW-1990 xenografts to nude mice, but inhibited CCK-stimulated growth transiently. Pancreastatin (100 micrograms/kg) transiently decreased volumes of MIA PaCa-2 xenografts to nude mice and significantly decreased weight, protein, and DNA of mouse pancreas. Fasting glucose levels of mice treated with pancreastatin 100 micrograms/kg for 35 days were significantly lower than controls. Our results demonstrate that pancreastatin not only inhibits CCK-stimulated pancreatic growth but also has inhibitory effects by itself.
Smith
J P
JP
Department of Medicine-Gastroenterology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033.
Kramer
S
S
Bagheri
S
S
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000494:pharmacology; D053379:Chromogranin A; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010187:Pancreatic Hormones / Q000494:pharmacology*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D053379:Chromogranin A; D010187:Pancreatic Hormones; D014316:Tritium; C050836:pancreastatin; D004247:DNA; D002766:Cholecystokinin; D013936:Thymidine