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Inhibitory and Stimulatory Effects of Glucocorticoid on Androgen-induced Growth of Murine Shionogi Carcinoma 115 in Vivo and in Cell Culture¹

Departments of Pathology [D. H., N. N., Y. N., K. M.], and Internal Medicine [B. S.], Osaka University Medical School, Kita-ku, Osaka 530; Shionogi Research Laboratory, Fukushima-ku, Osaka 553 [N. U.]; and Department of Surgery, The Center for Adult Diseases, Higashinari-ku, Osaka 537 [S. N.], Japan

It has been generally accepted for 20 years that the growth of Shionogi carcinoma 115 (SC115) is stimulated only by androgen in vivo and in cell culture. However, we recently found that the growth of SC115 is also stimulated by pharmacological, but not physiological, doses of glucocorticoid both in vivo and in cell culture and by pharmacological doses of estrogen only in vivo. In the present study, therefore, we investigated the effect of dexamethasone on androgen-induced growth of SC115 cells in vivo and in cell culture. In a serum-free medium [Ham's F-12:Eagle's minimum essential medium (1:1, v/v) containing 0.1% bovine serum albumin], the proliferation of SC-3 cells (a cloned cell line from SC115 cells) estimated by cell number and DNA synthesis reached a plateau at 10^-6 M testosterone (up to 93-fold) or 10^-6 M dexamethasone (up to 7.2-fold); high stimulation induced by higher than 10^-6 M testosterone was inhibited by the addition of 10^-5–10^-6 M dexamethasone in a concentration-dependent manner, whereas low stimulation induced by lower than 10^-10 M testosterone was significantly enhanced by the addition of dexamethasone. The presence of typical glucocorticoid and androgen receptors in SC-3 cells was also demonstrated; dexamethasone did not bind to androgen receptor and testosterone did not bind to glucocorticoid receptor. In castrated mice, the concomitant administration of dexamethasone again significantly inhibited the high growth of SC115 tumors induced by high doses of androgen but significantly enhanced the low growth induced by low doses of androgen. The present results demonstrate both inhibitory and stimulatory effects of glucocorticoid on androgen-induced proliferation of SC115 cells in cell culture and probably in vivo.

¹ Supported in part by a grant-in-aid for Cancer Research from the Ministry of Education, Science and Culture, and by a grant from the Japanese Foundation for Multidisciplinary treatment of cancer.

² To whom requests for reprints should be addressed.

Received 5/29/87. Revised 9/ 2/87. Accepted 9/18/87.