BINDING-STUDIES OF RU486 IN DIFFERENT REUBER HEPATOMA VARIANTS

The synthetic steroid RU486, which displays antiprogestin and antigluc ocorticoid properties in different systems, inhibits cell growth in de xamethasone-sensitive H56 cells containing glucocorticoid receptors, a s well as in dexamethasone-resistant S-H56-125 cells displaying a very low level of dexamethasone binding. In order to better understand the mechanism of the antiproliferative effect, the binding of RU486 to th ese hepatoma cells was examined. Results revealed the presence of two different kinds of binding sites for RU486 in dexamethasone-sensitive H56 cells whereas only one type of site was detected in the dexamethas one-resistant cells. These peculiar sites were also recognized by cort ivazol during competition experiments. Thus, it seems that S-H56-125 c ells contain an altered glucocorticoid receptor that binds RU486 and c ortivazol but virtually not dexamethasone. The ability of RU486 to inh ibit the growth of dexamethasone-resistant cells suggests this steroid may be used to treat tumor cells that develop glucocorticoid resistan ce after long-term treatment.