Glucocorticoids are widely used for cancer patients, although they can reduce the efficacy of anticancer treatment.

We characterized non-apoptotic actions of glucocorticoids on tumor cell lines, primary tumor cells and an in vivo model, together with molecular signaling studies.

Glucocorticoids enhanced cell proliferation in 9/17 cell lines and significantly promoted tumor cell proliferation in a pre-clinical mouse model of lung carcinoma. 65/139 primary acute childhood leukemia samples were glucocorticoid-resistant. Both dexamethasone and prednisolone increased in vitro survival in 21/65 samples from glucocorticoid-resistant primary leukemias, revealing a completely new action of glucocorticoids. Dexamethasone-induced proliferation was mediated by glucocorticoid receptor and activated the proliferation signaling pathways of protein kinase B/AKT and p38 mitogen-activated protein kinase.

Our data suggest that restriction of the use of glucocorticoids during anticancer treatment might improve the outcome of patients with solid tumors.