Growth-stimulating Effect of Pharmacological Doses of Glucocorticoid on Androgen-responsive Shionogi Carcinoma 115 in Vivo in Mice and in Cell Culture

It has been generally accepted for 20 years that the growth of Shionogi carcinoma 115 (SC115) is stimulated only by androgen. However, we recently found that the growth of SC115 cells is also stimulated by pharmacological doses of estrogen in vivo but not in cell culture. In the present study, the growth-stimulatory effect of glucocorticoid on SC115 cells was examined. In castrated mice, daily injections of high doses of dexamethasone (100 µg/mouse) markedly stimulated the tumor growth, and the growth approached that found in normal males. However, daily injections of physiological doses of dexamethasone (4 µg/mouse) or high doses of epitestosterone, progesterone, or cholesterol (200–5000 µg/mouse) did not enhance the tumor growth in castrated mice. The androgen dependency, growth speed, steroid receptors, and histological type of the tumors grown by pharmacological doses of glucocorticoid were not significantly different from those of the original SC115 tumors grown by androgen. 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) was markedly (by up to 25-fold) stimulated by 10-10-10-8 m testosterone, whereas the proliferation was only slightly but significantly (by up to 3.3-fold) stimulated by 10-8-10-5 m dexamethasone. The present findings demonstrate that the growth of SC115 cells in vivo and in cell culture is significantly stimulated by physiological doses of androgen or pharmacological doses of glucocorticoid.