Combined therapy with 5-azacytidine and hydrocortisone in glucocorticoid-sensitive and -resistant mouse P1798...

Experiments were undertaken to test the hypothesis that 5-azacytidine (AZA) treatment might make the glucocorticoid-resistant line of the mouse P1798 lymphosarcoma sensitive to cortisol. A modest (30%), though significant, effect in making cells cortisol sensitive was observed. Moreover, AZA enhanced tumor growth inhibition by cortisol in the corresponding sensitive line. The AZA alone was cytostatic, but it had no effect on DNA synthesis. The drug did not alter cytoplasmic glucocorticoid receptor levels or affinity, but nuclear levels were increased in the sensitive tumor. Results suggest that glucocorticoid resistance may be partially reversible and that the effect of AZA may be at the gene-expression level.