Glucocorticoids augment survival and proliferation of tumor cells.
BACKGROUND
Glucocorticoids are widely used for cancer patients, although they can reduce the efficacy of anticancer treatment.


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


RESULTS
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.


CONCLUSIONS
Our data suggest that restriction of the use of glucocorticoids during anticancer treatment might improve the outcome of patients with solid tumors.
Helmholtz Center Munich, German Research Center for Environmental Health, Munich, Germany.
Sibylle
S
Gündisch
Eva
E
Boeckeler
Uta
U
Behrends
Eberhard
E
Amtmann
Harald
H
Ehrhardt
Irmela
I
Jeremias
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002277:Carcinoma / Q000188:drug therapy; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003907:Dexamethasone / Q000009:adverse effects; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D007938:Leukemia / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011239:Prednisolone / Q000009:adverse effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D011239:Prednisolone; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases