垂体腺苷酸环化酶激活多肽对胰腺癌细胞的生长调控

目的 观察垂体腺苷酸环化酶激活多肽（pituitary adenylate cyclase activating polypeptide,PACAP)对人胰腺癌细胞株的生长调控作用；并确定神经鞘磷脂是否作为第二信使参与受体后信息传导。方法 人胰腺癌细胞株JF305，HS766T，ASPC－1进行细胞培养，传代。分别加入不同浓度的PACAP1－38（10^-6-10^-12mol/L)于三种癌细胞中。应用MTT法观察细胞增程度。薄层层析法测定细胞神经鞘磷脂。放射免疫法测定细胞内cAMP含量。Fura-2/AM测定细胞内游离Ca^2 浓度。结果 PACAP1－38促进JF305，HS766T，ASPC－1细胞的生长；PACAP1－38增加细胞内神经鞘磷脂、cAMP、Ca^2 的生长；生长抑素可明显抑制PACAP1－38诱导的JF305细胞的生长等作用。结论 PACAP1－38促进人胰腺癌细胞株的增殖。PACAP受体后信息传递途径；（1）腺苷 酸环化酶途径；（2）钙－钙调素途径。神经鞘磷脂作为第二信使也参与此过程。

The role of pituitary adenylate cyclase-activating polypeptide in the growth modulation of human pancreas carcinoma

Objective To investigate the role pituitary adenylate cyclase activating polypeptide (PACAP) in the growth modulation of PACAP of human pancreas carcinoma cells and determine whether sphingomyolin (SM) may act as a second messenger involved in the postreceptor signal transduction. Methods Human pancreas carcinoma cell strains, JF305, HS766T and ASPC 1 cells were cultivated, reproduced and then treated with PACAP 1 38 (10 -12 -10 -6 M). The amounts of proliferated carcinoma cells were estiimated with Mosmann's method (MTT). The concentrations of intracellular SM in cells were determined with thin layer chromotograph. Intracellular adenosine monophosphate and Ca 2 levels were detected by radioimmunoassay and Fura 2/AM respectively. Results It was found that three kind of human pancreatic cancer cells were proliferated and the intracellular levels of SM, cAMP and cytosolic Ca 2 were increased by treating PACAP 1 38 . The effect of PACAP 1 38 in JF305, HS766T and ASPC 1 could be inhibited by Somatostatin. Conclusion PACAP 1 38 may play a role in the proliferation of human pancreatic cancer cells. The postreceptorsignal transduction of PACAP may be mediated by both adenosine cyclinase and Calcium calmodin pathways. SM may be a second messenger involved in this process.