Inhibitory effect of a somatostatin analogue (SMS 201-995) on the growth of androgen-dependent mouse mammary tumor (Shionogi carcinoma 115).
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.
Noguchi
S
S
Department of Surgery, Center for Adult Diseases, Osaka.
Nishizawa
Y
Y
Motomura
K
K
Inaji
H
H
Imaoka
S
S
Koyama
H
H
Matsumoto
K
K
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D013006:Growth Hormone / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008815:Mice, Inbred Strains; D009368:Neoplasm Transplantation; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015282:Octreotide / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000032:analysis / Q000187:drug effects; D017481:Receptors, Somatostatin / Q000032:analysis / Q000187:drug effects; D013739:Testosterone / Q000378:metabolism; D014407:Tumor Cells, Cultured
D011944:Receptors, Androgen; D017481:Receptors, Somatostatin; D013739:Testosterone; D013006:Growth Hormone; D015282:Octreotide