Somatostatin analog RC-160 inhibits growth of CFPAC-1 human pancreatic cancer cells in vitro and intracellular production of cyclic adenosine monophosphate.
The effect of somatostatin analog RC-160 on the growth of CFPAC-1 human pancreatic cancer cells in vitro was investigated. RC-160 effectively inhibited the proliferation of CFPAC-1 cells in culture, inducing a time- and dose-dependent decrease in the number of treated cells. A significant suppression of cell growth was observed after 48 and 72 hr of the exposure to (1 microM) RC-160, the cell number being decreased by 38% and 46%, respectively. RC-160 was more potent than SS-14 or SMS201-995 in inhibiting the growth of CFPAC-1 cells, and after 48-hr treatment the cell number decreased by 49% for RC-160 compared with 12% for SS-14 and 27% for SMS201-995. Binding experiments demonstrated that specific receptors for somatostatin were present on CFPAC-1 cells. SS-14 showed a high binding affinity for [125I]-Tyr11-SS-14 receptors on CFPAC-1 cells. Scatchard analysis indicated the presence of 2 classes of somatostatin binding sites on the cells, one with high binding affinity and low capacity and the other with low binding affinity and high capacity. RC-160 could bind to somatostatin receptors on these cells with an affinity similar to SS-14 but significantly higher than that of SMS201-995. Radioimmunoassay of intracellular cAMP showed that RC-160 could powerfully inhibit forskolin-stimulated cAMP production in CFPAC-1 cells. Addition of forskolin to the cultures increased cAMP concentrations in the cellular lysate of treated cells. RC-160 attenuated or nullified in a dose-dependent manner the cAMP production stimulated by forskolin. Our observations indicate that somatostatin analog RC-160 inhibits the proliferation of CFPAC-1 human pancreatic cancer cells in vitro and that this effect may involve the intracellular cAMP pathway.
Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, LA 70146..
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D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000378:metabolism; D015282:Octreotide / Q000494:pharmacology; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017481:Receptors, Somatostatin / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009363:Neoplasm Proteins; D017481:Receptors, Somatostatin; D005576:Colforsin; C051458:vapreotide; D013004:Somatostatin; D000242:Cyclic AMP; D015282:Octreotide