Abstract
The effects of somatostatin (SRIF), insulin, and triiodothyronine (T3) on the growth of human hepatoma cells were investigated on the well-differentiated human hepatoma cell line Hep3B. Results showed that both insulin and T3 can stimulate cell growth of serum starved Hep3B cells at physiological concentrations. SRIF alone showed little growth-promoting activity. When added concurrently with insulin, however, SRIF suppressed the insulin-induced cell proliferation in a dose-dependent manner. On the other hand, SRIF had no inhibitory effect on T3-induced cell proliferation. SRIF is labile in the medium, with a half-life of about 2 h during culture incubation. SRIF did not disturb the insulin binding to its surface receptors nor inhibit the insulin-dependent receptor kinase activity of Hep3B cells in vitro. These results suggest that postreceptor regulation may be involved. The selective suppression by SRIF of insulin-induced cell growth provides an unique approach to the study of insulin actions on proliferation of human hepatoma cells.
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- Aden D. P., Fogel A., Plotkin S., Damjanov I., Knowles B. B. Controlled synthesis of HBsAg in a differentiated human liver carcinoma-derived cell line. Nature. 1979 Dec 6;282(5739):615–616. doi: 10.1038/282615a0. [DOI] [PubMed] [Google Scholar]
- Aguilera G., Parker D. S., Catt K. J. Characterization of somatostatin receptors in the rat adrenal glomerulosa zone. Endocrinology. 1982 Oct;111(4):1376–1384. doi: 10.1210/endo-111-4-1376. [DOI] [PubMed] [Google Scholar]
- Brazeau P., Vale W., Burgus R., Ling N., Butcher M., Rivier J., Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science. 1973 Jan 5;179(4068):77–79. doi: 10.1126/science.179.4068.77. [DOI] [PubMed] [Google Scholar]
- Bucher M. L., Swaffield M. N. Regulation of hepatic regeneration in rats by synergistic action of insulin and glucagon. Proc Natl Acad Sci U S A. 1975 Mar;72(3):1157–1160. doi: 10.1073/pnas.72.3.1157. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cuatrecasas P. Insulin--receptor interactions in adipose tissue cells: direct measurement and properties. Proc Natl Acad Sci U S A. 1971 Jun;68(6):1264–1268. doi: 10.1073/pnas.68.6.1264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Flier J. S., Usher P., Moses A. C. Monoclonal antibody to the type I insulin-like growth factor (IGF-I) receptor blocks IGF-I receptor-mediated DNA synthesis: clarification of the mitogenic mechanisms of IGF-I and insulin in human skin fibroblasts. Proc Natl Acad Sci U S A. 1986 Feb;83(3):664–668. doi: 10.1073/pnas.83.3.664. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harrison L. C., Itin A. Purification of the insulin receptor from human placenta by chromatography on immobilized wheat germ lectin and receptor antibody. J Biol Chem. 1980 Dec 25;255(24):12066–12072. [PubMed] [Google Scholar]
- Heisler S., Reisine T. D., Hook V. Y., Axelrod J. Somatostatin inhibits multireceptor stimulation of cyclic AMP formation and corticotropin secretion in mouse pituitary tumor cells. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6502–6506. doi: 10.1073/pnas.79.21.6502. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ho L. T., Chen R. L., Chou T. Y., Fong J. C., Wang P. S., Chou C. K. Pharmacokinetics and effects of intravenous infusion of somatostatin in normal subjects--a two-compartment open model. Clin Physiol Biochem. 1986;4(4):257–267. [PubMed] [Google Scholar]
- Jaspan J., Polonsky K., Lewis M., Moossa A. R. Reduction in portal vein blood flow by somatostatin. Diabetes. 1979 Oct;28(10):888–892. doi: 10.2337/diab.28.10.888. [DOI] [PubMed] [Google Scholar]
- Kahn C. R. The molecular mechanism of insulin action. Annu Rev Med. 1985;36:429–451. doi: 10.1146/annurev.me.36.020185.002241. [DOI] [PubMed] [Google Scholar]
- King G. L., Kahn C. R., Rechler M. M., Nissley S. P. Direct demonstration of separate receptors for growth and metabolic activities of insulin and multiplication-stimulating activity (an insulinlike growth factor) using antibodies to the insulin receptor. J Clin Invest. 1980 Jul;66(1):130–140. doi: 10.1172/JCI109826. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Koch B. D., Dorflinger L. J., Schonbrunn A. Pertussis toxin blocks both cyclic AMP-mediated and cyclic AMP-independent actions of somatostatin. Evidence for coupling of Ni to decreases in intracellular free calcium. J Biol Chem. 1985 Oct 25;260(24):13138–13145. [PubMed] [Google Scholar]
- Kulkarni P. G., Hoffman F. M., Shoemaker R. L. Inhibition of H+ secretion in frog gastric mucosa by somatostatin. Am J Physiol. 1979 Jun;236(6):E784–E787. doi: 10.1152/ajpendo.1979.236.6.E784. [DOI] [PubMed] [Google Scholar]
- Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
- Leffert H. L., Koch K. S., Moran T., Rubalcava B. Hormonal control of rat liver regeneration. Gastroenterology. 1979 Jun;76(6):1470–1482. [PubMed] [Google Scholar]
- Oppenheimer J. H. Thyroid hormone action at the cellular level. Science. 1979 Mar 9;203(4384):971–979. doi: 10.1126/science.218285. [DOI] [PubMed] [Google Scholar]
- Orci L., Unger R. H. Functional subdivision of islets of Langerhans and possible role of D cells. Lancet. 1975 Dec 20;2(7947):1243–1244. doi: 10.1016/s0140-6736(75)92078-4. [DOI] [PubMed] [Google Scholar]
- Schusdziarra V., Harris V., Arimura A., Unger R. H. Evidence for a role of splanchnic somatostatin in the homeostasis of ingested nutrients. Endocrinology. 1979 Jun;104(6):1705–1708. doi: 10.1210/endo-104-6-1705. [DOI] [PubMed] [Google Scholar]
- Schusdziarra V., Harris V., Conlon J. M., Arimura A., Unger R. Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog. J Clin Invest. 1978 Sep;62(3):509–518. doi: 10.1172/JCI109154. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Short J., Brown R. F., Husakova A., Gilbertson J. R., Zemel R., Lieberman I. Induction of deoxyribonucleic acid synthesis in the liver of the intact animal. J Biol Chem. 1972 Mar 25;247(6):1757–1766. [PubMed] [Google Scholar]
- Van Wyk J. J., Graves D. C., Casella S. J., Jacobs S. Evidence from monoclonal antibody studies that insulin stimulates deoxyribonucleic acid synthesis through the type I somatomedin receptor. J Clin Endocrinol Metab. 1985 Oct;61(4):639–643. doi: 10.1210/jcem-61-4-639. [DOI] [PubMed] [Google Scholar]
- Webb S., Kravetz D., Bosch J., Wass J. A., Evans J., Gomis R., Rees L. H., Rodés J. Splanchnic and hepatic metabolism of somatostatin: a study in cirrhotic patients with a portacaval shunt. Hepatology. 1983 Mar-Apr;3(2):193–197. doi: 10.1002/hep.1840030210. [DOI] [PubMed] [Google Scholar]
- Zyznar E. S., Pietri A. O., Harris V., Unger R. H. Evidence for the hormonal status of somatostatin in man. Diabetes. 1981 Oct;30(10):883–886. doi: 10.2337/diab.30.10.883. [DOI] [PubMed] [Google Scholar]

