The effect of gastrointestinal hormones on the incorporation of tritiated thymidine in the pancreatic adenocarcinoma cell line (WD PaCa).
In view of the trophic action of gastrointestinal hormones on the exocrine pancreas, the effects of secretin, octapeptide of cholecystokinin (CCK-8), and desglugastrin on the growth of hamster pancreatic well differentiated adenocarcinoma were investigated in vitro. Desglugastrin exhibited the greatest effect on thymidine incorporation into these cells after a lag period of 96 h. Doses of desglugastrin in the range from 30 to 270 ng/mL caused a significant and dose-dependent increase in thymidine incorporation. Higher doses of this peptide led to a decreased response. Secretin also increased thymidine incorporation, but the response was less than that induced by gastrin. Prolonged incubation with secretin for 96 h increased tritiated thymidine incorporation in a log-dose fashion in the range of 30 to 270 ng/mL. Doses of CCK-8 in the range of 90 to 810 ng/mL significantly increased thymidine incorporation after 48 h of incubation. Following 72 h of incubation, only the dose of 270 ng/mL continued to exhibit a significant stimulation. Our study suggests that the gastrointestinal hormones could directly increase the growth of pancreatic carcinoma cells, act synergistically with endogenous growth factors, or stimulate the local production of these factors. In any event, our results that gastrin, secretin, and CCK can stimulate the growth of pancreatic ductal tumor cells in tissue cultures, support earlier findings on normal and malignant pancreatic parenchyma.
Edwards
B F
BF
Endocrine, Polypeptide, Veterans Administration Medical Center, New Orleans, LA.
Redding
T W
TW
Schally
A V
AV
D000230:Adenocarcinoma; D000595:Amino Acid Sequence; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004261:DNA Replication / Q000187:drug effects*; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D005755:Gastrins / Q000494:pharmacology*; D007700:Kinetics; D008969:Molecular Sequence Data; D010190:Pancreatic Neoplasms; D012633:Secretin / Q000494:pharmacology*; D012844:Sincalide / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014316:Tritium
D004273:DNA, Neoplasm; D005755:Gastrins; D014316:Tritium; D012633:Secretin; C062105:desglugastrin; D012844:Sincalide; D013936:Thymidine