Inhibitory effect of a somatostatin analogue (SMS 201-995) on the growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115). 1993

S Noguchi, and Y Nishizawa, and K Motomura, and H Inaji, and S Imaoka, and H Koyama, and K Matsumoto
Department of Surgery, Center for Adult Diseases, Osaka.

The influence of a somatostatin analogue, SMS 201-995 (SMS), on the growth of an androgen-dependent mouse mammary tumor, Shionogi carcinoma 115 (SC115), was studied. Treatment of SC115 tumor-transplanted male mice with s.c. injections of SMS (0.04, 0.2, 1, and 5 micrograms twice a day) resulted in a dose-dependent inhibition of tumor growth. The growth-inhibitory effect of SMS reached its peak at a dose of 1 microgram twice a day. SMS was found not to elicit its growth-inhibitory effect through lowering plasma testosterone levels or down-regulating androgen receptor of SC115 tumors. Since specific binding sites for somatostatin were not observed in the membrane fractions of SC115 tumors and SMS did not inhibit the proliferation of primarily cultured SC115 tumor cells, a direct inhibitory mechanism of SMS on SC115 tumors was unlikely to be operative. Since SMS is a very potent inhibitor of growth hormone (GH) secretion, it was speculated that SMS might inhibit the growth of SC115 tumors indirectly through down-regulation of plasma GH levels. This possibility was evaluated by studying the influence of GH replacement on the growth of SC115 tumors grown in SMS-treated mice. GH replacement was done both in a male secretory pattern (intermittent injection, human GH 500 micrograms/kg twice a day) and in a female secretory pattern (continuous infusion, 1000 micrograms/kg/day). Intermittent injections of GH fully restored the growth of SC115 tumors in the SMS-treated mice to that in the normal controls but continuous infusion of GH was without effect. These results suggest that SMS inhibits the growth of SC115 tumors through suppression of GH secretion, and that the mode of GH administration is an important determinant of its action on SC115 tumor growth.

UI MeSH Term Description Entries
D008297 Male Males
D008325 Mammary Neoplasms, Experimental Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS. Experimental Mammary Neoplasms,Neoplasms, Experimental Mammary,Experimental Mammary Neoplasm,Mammary Neoplasm, Experimental,Neoplasm, Experimental Mammary
D008815 Mice, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations, or by parent x offspring matings carried out with certain restrictions. All animals within an inbred strain trace back to a common ancestor in the twentieth generation. Inbred Mouse Strains,Inbred Strain of Mice,Inbred Strain of Mouse,Inbred Strains of Mice,Mouse, Inbred Strain,Inbred Mouse Strain,Mouse Inbred Strain,Mouse Inbred Strains,Mouse Strain, Inbred,Mouse Strains, Inbred,Strain, Inbred Mouse,Strains, Inbred Mouse
D009368 Neoplasm Transplantation Experimental transplantation of neoplasms in laboratory animals for research purposes. Transplantation, Neoplasm,Neoplasm Transplantations,Transplantations, Neoplasm
D009376 Neoplasms, Hormone-Dependent Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment. Hormone-Dependent Neoplasms,Hormone Dependent Neoplasms,Hormone-Dependent Neoplasm,Neoplasm, Hormone-Dependent,Neoplasms, Hormone Dependent
D011944 Receptors, Androgen Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA. Androgen Receptors,5 alpha-Dihydrotestosterone Receptor,Androgen Receptor,Dihydrotestosterone Receptors,Receptor, Testosterone,Receptors, Androgens,Receptors, Dihydrotestosterone,Receptors, Stanolone,Stanolone Receptor,Testosterone Receptor,5 alpha Dihydrotestosterone Receptor,Androgens Receptors,Receptor, 5 alpha-Dihydrotestosterone,Receptor, Androgen,Receptor, Stanolone,Stanolone Receptors,alpha-Dihydrotestosterone Receptor, 5
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013006 Growth Hormone A polypeptide that is secreted by the adenohypophysis (PITUITARY GLAND, ANTERIOR). Growth hormone, also known as somatotropin, stimulates mitosis, cell differentiation and cell growth. Species-specific growth hormones have been synthesized. Growth Hormone, Recombinant,Pituitary Growth Hormone,Recombinant Growth Hormone,Somatotropin,Somatotropin, Recombinant,Growth Hormone, Pituitary,Growth Hormones Pituitary, Recombinant,Pituitary Growth Hormones, Recombinant,Recombinant Growth Hormones,Recombinant Pituitary Growth Hormones,Recombinant Somatotropins,Somatotropins, Recombinant,Growth Hormones, Recombinant,Recombinant Somatotropin
D013739 Testosterone A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL. 17-beta-Hydroxy-4-Androsten-3-one,17-beta-Hydroxy-8 alpha-4-Androsten-3-one,8-Isotestosterone,AndroGel,Androderm,Andropatch,Androtop,Histerone,Sterotate,Sustanon,Testim,Testoderm,Testolin,Testopel,Testosterone Sulfate,17 beta Hydroxy 4 Androsten 3 one,17 beta Hydroxy 8 alpha 4 Androsten 3 one,8 Isotestosterone

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