Silodosin is a novel, more selective alpha-blocker, which is specific to the lower urinary tract and may have fewer side effects than other alpha-blockers[3]. Silodosin potently inhibits 2-[2-(4-hydroxy-3-[125I]iodophenyl)ethylaminomethyl]-alpha-tetralone binding to the cloned human alpha 1a-AR, with a Ki value of 0.036 nM, but has 583- and 56-fold lower potency at the alpha 1b- and alpha 1d-ARs, respectively[4]. Silodosin determines smooth muscle relaxation in bladder and prostate tissues, increases bladder blood flow in conditions of chronic bladder ischemia and regulates the activity of transcriptional factors responsible for stromal growth and prostate hyperplasia. Silodosin is one of the drugs approved for the treatment of BPH (benign prostatic hyperplasia), being highly effective in improving not only LUTS (lower urinary tract symptoms) but also urodynamic parameter impairments secondary to BPH[5]. In bladder cancer cell lines, silodosin reduced the expression of ELK1 (mRNA/protein) and its downstream target, c-fos gene, as well as the transcriptional activity of ELK1. Silodosin also inhibited the migration of ELK1-positive cells with or without a functional AR, but not that of ELK1 knockdown cells. Combined treatment with silodosin is useful for overcoming chemoresistance in patients with ELK1-positive urothelial carcinoma receiving cisplatin[6].
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