Differential regulation of bladder cancer growth by various glucocorticoids: corticosterone and prednisone inhibit cell invasion without promoting cell proliferation or reducing cisplatin cytotoxicity
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A synthetic glucocorticoid, dexamethasone, was recently shown to inhibit bladder cancer cell invasion and metastasis through the glucocorticoid receptor (GR) pathway but increased cell proliferation via inhibiting apoptosis particularly induced by cisplatin. Therefore, comedication with dexamethasone in bladder cancer patients may lead to unfavorable outcomes such as chemoresistance. We here look for any glucocorticoids with inhibitory effects on tumor cell invasion yet inhibitory or at least no stimulatory effects on cell viability.
The effects of 10 glucocorticoids on cell viability were first assessed in three bladder cancer lines. Selected compounds were further assessed for their ability in cell viability and apoptosis, with or without cisplatin, as well as in cell invasion.
Most of the compounds (hydrocortisone, betamethasone, flumethasone, triamcinolone, budesonide, fluticasone propionate, and fludrocortisone acetate) increased GR-positive cell growth, which was similar to or even stronger than the effect of dexamethasone. Nonetheless, two glucocorticoids (corticosterone, prednisone) showed only marginal effects on cell growth of all the lines tested. They did not significantly reduce the effects of cisplatin on cell proliferation or cisplatin-induced apoptosis. Conversely, corticosterone, prednisone, and dexamethasone similarly inhibited cell invasion and expression of related genes, including MMP-9, VEGF, and IL-6, in GR-positive lines.
Corticosterone and prednisone are suggested to have the potential of being harmless, in contrast to dexamethasone, without promoting cell proliferation or inhibiting cytotoxic activity of cisplatin, yet beneficial to bladder cancer patients via suppressing tumor invasion. Our results are thus useful in improving chemotherapy regimens, including optimal glucocorticoids, for urothelial carcinoma.
KeywordsBladder cancer Chemotherapy Cisplatin Comedication Glucocorticoids
Conflict of interest
The authors declare that they have no conflict of interest.
- 7.Ishiguro H, Kawahara T, Li Y, Miyamoto H (2013) Anti-tumor activities of dexamethasone. In: Sauvage A, Levy M (eds) Dexamethasone: therapeutic uses, mechanism of action and potential side effects. Nova Science Publishers, New York, pp 117–135Google Scholar
- 9.Ishiguro H, Kawahara T, Zheng Y, Netto GJ, Miyamoto H (2014) Reduced glucocorticoid receptor expression predicts bladder tumor recurrence and progression. Am J Clin Pathol (in press)Google Scholar
- 15.Domingo-Domenech J, Oliva C, Rovira A et al (2006) Interleukin 6, a nuclear factor-κB target, predicts resistance to docetaxel in hormone-independent prostate cancer and nuclear factor-κB inhibition by PS-1145 enhances docetaxel antitumor activity. Clin Cancer Res 12:5578–5586PubMedCrossRefGoogle Scholar
- 21.Singer M, Webb AR (2005) Oxford handbook of critical care, 2nd edn. Oxford University Press, New YorkGoogle Scholar