Effects of glucocorticoids on the growth of human fibrosarcoma cell line HT-1080.

The human fibrosarcoma cell line HT-1080 exhibits rapid growth following s.c. inoculation in 4-6-week-old male athymic mice. Cytosols from tumors carried in athymic mice bind glucocorticoid (Kd, 1.8 +/- 0.48 X 10(-8) M; Bmax, 240.5 +/- 35.3 fmol/mg cytosol protein, mean +/- SEM). Receptor sediments primarily in the 8-9S region on 5-20% sucrose gradients and is specific for the glucocorticoids. HT-1080 growth in vitro (as measured by cell count) was inhibited over a range of 10(-6)-10(-8) M after 7 days of incubation with dexamethasone and triamcinolone acetonide. Progesterone, estradiol, and dihydrotestosterone had no effect on HT-1080 growth in vitro. Preincubation with a 100-fold excess of progesterone reversed the growth inhibition observed with triamcinolone acetonide but not dexamethasone acetate. HT-1080 tumor cell growth responded biphasically to dexamethasone in vivo. Athymic mice given s.c. injections every other day with 5 or 25 micrograms dexamethasone showed an increase in tumor size inversely proportional to dose. In contrast, 200 micrograms of dexamethasone significantly inhibited tumor growth. Adrenalectomy did not significantly alter HT-1080 growth or glucocorticoid binding to tumor cytosols (Kd, 3.4 X 10(-8) +/- 1.1, Bmax, 236.9 +/- 9.9 fmol/mg cytosol protein, mean +/- SEM) although tumor incidence was decreased in sham adrenalectomized mice. Glucocorticoid binding in tumors grown in vivo was decreased by increasing amounts of dexamethasone. High pharmacological doses of glucocorticoids inhibit the growth of human fibrosarcomas in vivo and in vitro.