morphinans and Urinary-Bladder-Neoplasms

P-Glycoprotein-mediated multidrug resistance is a frequent event during chemotherapy and a key obstacle for bladder cancer therapy. Search for strategies to reverse multidrug resistance is a promising approach to improve the management of bladder cancer. In the present study, we reported a novel P-glycoprotein-mediated multidrug resistant cell model 253J/DOX, which was generated from human bladder cancer 253J cell line. Furthermore, we found that the multidrug resistant phenotype of 253J/DOX cells could be overcome by sinomenine, an alkaloid derived from the stem of Sinomenium acutum. Mechanistically, the chemosensitive effect by sinomenine was mediated by down-regulating P-glycoprotein expression, as well as triggering apoptotic pathways. The chemosensitive effect of sinomenine may make it a prime candidate agent to target bladder cancer.

Topics: Apoptosis; ATP Binding Cassette Transporter, Subfamily B, Member 1; Blotting, Western; Cell Line, Tumor; Coloring Agents; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Flow Cytometry; Fluorescent Antibody Technique; Fluorescent Dyes; Humans; Indicators and Reagents; Morphinans; Real-Time Polymerase Chain Reaction; Rhodamine 123; RNA, Small Interfering; Tetrazolium Salts; Thiazoles; Urinary Bladder Neoplasms