MRS1754 inhibits proliferation and migration of bladder urothelial carcinoma by regulating mitogen-activated protein kinase pathway.

Bladder urothelial carcinoma (BUC) is one of the most common urological malignancies. Our previous study found that adenosine A2b receptor (A2bR) was upregulated in BUC tissues and cells. In the present study, we investigated the effect of MRS1754 (a selective A2bR antagonist) on cell proliferation and migration in two well-studied invasive urothelial cell carcinoma lines EJ and T24. Our results showed that MRS1754 reduced BUC cell proliferation and induced a G0/G1 phase cell-cycle arrest. Next, MRS1754 inhibited cell migration and Bay60-6583 (a selective A2bR agonist) treatment could reverse the inhibitory effect of MRS1754 on BUC cells migration. Furthermore, our results showed MRS1754 treatment downregulated the protein levels of p-P38, p-JNK, and phospho-extracellular signal-regulated kinase (p-ERK). These findings suggest that MRS1754 can inhibit progression of BUC via mitogen-activated protein kinase (MAPK) pathway and indicate the therapeutic potential of A2B antagonists in BUC.