Somatostatin receptor subtype 1-selective activation reduces cell growth and calcitonin secretion in a human medullary thyroid carcinoma cell line.
Medullary thyroid carcinoma (MTC) is a rare and aggressive tumor and so far medical therapy has provided inconclusive results. In the human MTC cell line TT, expressing all somatostatin (SST) receptor subtypes, cell proliferation decreases with SST and SST receptor subtype 2 (sst(2)), but not sst(5), selective agonist treatment, whereas calcitonin (CT) expression and secretion are reduced by SST, but not by sst(2) and sst(5) agonists. The effectiveness of two new SST analogs, BIM-23926 and BIM-23745, selectively interacting with sst(1), was investigated in the TT cell line. DNA synthesis is significantly reduced by BIM-23926 (27-40% at 10(-10)-10(-6)M) and BIM-23745 (32-90% at 10(-8)-10(-6)M). Viable cell number is also significantly reduced by both BIM-23926 (40% at 10(-12)-10(-6)M) and BIM-23745 ( approximately 40% at 10(-10)-10(-6)M). Treatment with sst(1)-selective agonists significantly reduces CT secretion and gene expression, with a reduction of CREB phosphorylation. These findings suggest that potent sst(1)-selective agonists could have a therapeutic role in MTC.
D001483:Base Sequence; D002116:Calcitonin / Q000235:genetics / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D005576:Colforsin / Q000494:pharmacology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D017931:DNA Primers; D004261:DNA Replication / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D017481:Receptors, Somatostatin / Q000819:agonists* / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000378:metabolism; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D013964:Thyroid Neoplasms; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
C519494:BIM 23926; D017362:Cyclic AMP Response Element-Binding Protein; D017931:DNA Primers; D017481:Receptors, Somatostatin; D011994:Recombinant Proteins; C101130:somatostatin receptor type 1; D005576:Colforsin; D013004:Somatostatin; D002116:Calcitonin