Introduction: Chemotherapy-induced nausea is commonly treated by administration of glucocorticoids, which are also known to influence tumour cell behaviour. We have previously identified a class effect of glucocorticoids inhibiting serum-induced migration in the human breast tumour cell line, MDA-MB-231, in a 2-dimensional scrape wound healing assay and a 3-dimensional modified Boyden chamber assay. This glucocorticoid effect appears to be dependent on transactivation rather than transrepression. Interestingly, the murine breast tumour cell line, 4T1.2, showed dex-induced inhibition of migration in the 3-dimensional but not 2-dimensional migration assays.
Aims: To investigate the effect of glucocorticoids in a mouse model of breast cancer.
Methods: mCherry-expressing 4T1.2 murine breast tumour cells (500,000) were injected into the 4thmammary fat pad of Balb-c mice. Dexamethasone (dex) was administered sc at 0.1mg/kg/day, commencing 2 days after the tumour was first palpable. Primary tumour and organs were harvested after a further 23 days. DNA was extracted from lung, spine and femur using phenol-chloroform and levels of mCherry were measured using qPCR along with vimentin as a control. mCherry content was assessed as a measure of metastasis.
Results: Dex treatment reduced final body weight (Vehicle: 19±0.3g, Dex: 18±0.3g, P<0.05) but there was no affect on primary tumour weight. There was a significant increase in mCherry content (metastasis) in the lungs of dex-treated mice (Vehicle: 1.0±0.3, Dex: 2.0±0.6, P<0.05).
Discussion: Dexamethasone had no effect on primary tumour growth but increased metastasis to the lung. This effect was opposite to expectations based on previous in vitro studies. Our findings suggest Dex may promote tumour spread. Confirmation of these findings in xenograft models of human breast tumours in mice would lead us to advocate for the use of other non-steroidal anti-emetics in treating breast cancer.