The Effect of Gastrin and Cholecystokinin on the Growth of Pancreato-biliary Cancer Cell Lines

ABSTRACT

PURPOSE: Gastrin and cholecystokinin (CCK) have been reported to play a role in the development and growth stimulation of gastrointestinal cancers including pancreatic cancer. METHODS: We investigated the effects of gastrin and CCK on the growth of pancreatic and biliary tract cancer cell lines established at the Cancer Research Institute of Seoul National University College of Medicine, using reverse transcription-polymerase chain reaction (RT-PCR) and slot blot hybridization, to examine the expressions of hormonal receptors in these cell lines. RESULTS: Of the six biliary tract, and five pancreatic, cancer cell lines, SNU-308 showed a growth stimulated effect due to gastrin-17, as did SNU-478 to both gastrin-17 and CCK-8. The trophic effect of these two hormones was completely blocked by specific antagonists (L-365, 260 for gastrin and L-364, 718 for CCK). The other cell lines did not respond to either the gastrin or the CCK. From the RT-PCR, the presence of the CCK-A receptor and the CCK-B/gastrin receptor mRNA was detected in all the biliary and pancreatic cancer cell lines. From the slot blot hybridization, although the cell lines that responded to the hormones showed high level of expression for receptor mRNA, so did some of those not responding to the hormones. CONCLUSION: This study suggests that gastrin and CCK exert a trophic action on some biliary tract cancers due to their specific receptors. However, further studies investigating the functional and structural variation among these receptors, in relation to their subtypes and mutation/polymorphism are requisite prior to their clinical usage for adjunctive hormonal or antihormonal therapy can be recommended.