The Role of Phenethyl Isothiocyanate on Bladder Cancer ADM Resistance Reversal and Its Molecular Mechanism

Abstract

Adramycin (ADM) resistance is an essential aspect of bladder cancer treatment failure and phenethyl isothiocyanate (PEITC) has been found to exhibit antitumor properties; however, the effect and potential mechanism of PEITC on bladder cancer ADM resistance reversal is not fully clear. The aim of this study was to explore the role of PEITC in bladder cancer cells ADM resistance reversal and the underlying molecular mechanisms. In this report, we identified the role of PEITC on ADM resistance reversal of human bladder carcinoma T24/ADM cells, including an increased drug sensitivity to ADM, cell apoptosis rates, intracellular accumulation of Rhodamine-123 (Rh-123), an increased expression of DNA topoisomerase II (Topo-II), and a decreased expression of multidrug resistance gene (MDR1), multidrug resistance-associated protein (MRP1), bcl-2 and glutathione s transferase π (GST-π).We also found that there was a decreased expression of NF-κB, Survivin, Twist, and p-Akt, and an increased expression of PTEN and p-JNK after PEITC treatment for T24/ ADM cells. The results indicated that PEITC might be used as a potential therapeutic strategy to ADM resistance through blocking Akt and activating MAPK pathway in human bladder carcinoma.