Role of 5-Aza-CdR in mitomycin-C chemosensitivity of T24 bladder cancer cells

摘要

Chemotherapeutic insensitivity is one of key obstacles to effectively treating muscle invasive bladder cancer. 5-Aza-2′-deoxycytidine (5-Aza-CdR) has been identified as a tumor suppressive agent in various types of cancer. The aim of the present study was to identify the effects of 5-Aza-CdR on the mitomycin-C (MMC) chemosensitivity of T24 bladder cancer cells and investigate the underlying mechanisms. T24 cells were treated with a combination of MMC and 5-Aza-CdR at various concentrations. The rates of proliferation and apoptosis were assessed by an MTT assay and flow cytometry, respectively. The expression of drug resistance-associated proteins, including P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1), and autophagy-associated proteins, including beclin 1, nucleoporin 62 (p62) and autophagy protein 5 (ATG5) were detected with western blotting. Treatment with 5-Aza-CdR significantly promoted the MMC chemosensitivity of T24 cells. The proliferation of T24 cells was significantly inhibited with increasing 5-Aza-CdR concentration, whereas apoptosis was significantly increased. This was associated with the decreased expression of P-gp, MRP1, beclin 1, p62 and ATG5. In conclusion, 5-Aza-CdR enhanced MMC chemosensitivity in bladder cancer T24 cells, which may be caused by the suppression of drug resistance- and autophagy-associated proteins.