Regulation Of Bladder Cancer Stem Cell By Dexamethasone- Mediated Glucocorticoid Receptor Signals

In patients with advanced bladder cancer, glucocorticoids are frequently given to reduce acute toxicity, particularly hyperemesis, during chemotherapy, as well as to improve cachectic conditions. However, it remains unclear whether glucocorticoids directly affect the development and progression of bladder cancer through the glucocorticoid receptor pathway. Glucocorticoid receptor expression was first investigated in human bladder cancer lines and tissue microarrays. Then, the effects of dexamethasone on glucocorticoid receptor transcription, cell proliferation, apoptosis/cell cycle, and invasion were examined in bladder cancer lines. All the cell lines and tissues examined were found to express glucocorticoid receptor. Dexamethasone increased glucocorticoid receptor-mediated reporter activity and cell proliferation, and inhibited apoptosis in the presence or absence of cisplatin. In contrast, dexamethasone suppressed cell invasion, the expression of its related tumor stem cell markers [CD133,CD44], and the activity of them, also induced mesenchymal-to-epithelial transition.Thus, glucocorticoid receptor activation resulted in promotion of cell proliferation via inhibiting apoptosis yet repression of cell invasion and metastasis. These results may provide a basis of developing improved chemotherapy regimens, including or excluding glucocorticoid receptor agonists/antagonists, for urothelial carcinoma. Dexamethasone was now 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, since we have proved the thetumer stem cell markers’ impression could increase a lot after treatment in our research.