Glucocorticoid-induced growth inhibition of cells from a human lung alveolar cell carcinoma.

We have studied the effects of dexamethasone on cell growth and DNA synthesis in the A549 cell line, a line that was originally isolated from a human alveolar carcinoma. Dexamethasone at a concentration of 10 9 M inhibited growth of these cells. Maximal growth inhibition was seen with 4 x 10 " M dexamethasone (44% of control). The population-doubling time of the cells increased from 28.4 hr under control conditions to 66.5 hr with dexamethasone treatment. Dexamethasone also inhibited DNA synthesis within the same concentration range that inhibited cell growth. Decreased [3H]thymidine incorporation was ob served as early as 6 hr after steroid addition. Inhibition of growth and DNA synthesis by other steroids was observed and was of the order: dexamethasone > cortisol > corti costerone > deoxycortisone. Testosterone and estradici were not inhibitory. The cells were also examined for presumptive evidence of cytoplasmic [3H]dexamethasone receptors. Specific binding of [3H]dexamethasone was observed, and Scatchard analysis of the data revealed that K,¡ equalled 7.1 x 10 9 M. The ability of other steroids to decrease the binding of [3H]dexamethasone was re lated to their ability to inhibit A549 cell growth and their biological activity as glucocorticoids. We feel that the A549 cell line will provide a system in which to study a pattern of glucocorticoid-induced growth inhibition that is not associated with marked catabolic effects and cell lysis and that may provide a model for the study of the relation ship of steroid-induced differentiation to growth.