Abstract #768: Tumor cell proliferation as new adverse effect of glucocorticoids

AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO During chemotherapy, glucocorticoids are often used as adjuvants due to their multiple functions as anti-emetics or anti-edematous agents among others. In the special case of lymphoid tumors, glucocorticoids act as anti-tumor agents. In contrast to their beneficial effects on non-tumor cells, anti-apoptotic effects of glucocorticoids towards tumor target cells were reported, e.g., as glucocorticoids reduced the anti-cancer effect of cisplatin in cancer cell lines both in vitro and in vivo. Here we show that glucocorticoids exert a new, yet unknown side effect directed against tumor cells: Glucocorticoids induce the growth of tumor cells resistant against cell death induction by glucocorticoids. Induction of proliferation was shown in many tumor cell lines of different origin and measured using various techniques such as MTT assay, cell count, ATP-based cell viability assay, BrdU incorporation among others. Glucocorticoid-induced tumor cell proliferation was found even in the presence of additional cytotoxic drugs. In an animal model of subcutaneous growing lung cancer cells, dexamethason significantly enhanced tumor growth. Glucocorticoids induced tumor cell proliferation by activation of classical proliferation kinases which was inhibited, when these pathways were blocked. This is the first report showing that glucocorticoids induce tumor cell proliferation and thereby exert direct negative effects against tumor cells. Our data suggest that glucocorticoids should be used with major caution during anti-cancer therapy. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 768.