Role of pituitary adenylate cyclase-activating polypeptide in the growth modulation of human pancreatic carcinoma

OBJECTIVE: To investigate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the growth modulation of human pancreatic carcinoma and to determine whether sphingomyelin may act as a second messenger in post-receptor signal transduction. METHODS: Three human pancreatic cancer cell lines, JF305, HS766T and ASPC-1, were cultivated, propagated and then treated with various concentrations of PACAP1–38 (10–12–10–6 mol/L). The number of proliferating cancer cells was estimated by using Mosmann’s MTT method. The concentration of intracellular sphingomyelin was determined by thin layer chromatography. Levels of intracellular adenosine monophosphate and Ca2+ were measured by radioimmunoassay and Fura-2/AM, respectively. RESULTS: The proliferation of human pancreatic cancer cell lines was enhanced and the intracellular levels of sphingomyelin, cAMP and cytosolic Ca2+ were increased by treatment with PACAP1–38. The effect of PACAP1–38 on JF305, HS766T and ASPC-1 cells was inhibited by somatostatin. CONCLUSIONS: It is possible that PACAP1–38 plays a role in the proliferation of human pancreatic cancer cells. The post-receptor signal transduction of PACAP may be mediated by both the adenosine cyclinase and calcium–calmodulin pathways. Sphingomyelin may be a second messenger involved in this process.