Cordycepin reverses cisplatin resistance in human bladder cancer cells via the PTEN/PI3K/AKt pathway

Abstract

Purpose: To study the influence of cordycepin (Cor) on cisplatin insensitivity in bladder carcinoma, and its underlying mechanism of action.Methods: The effects of cisplatin and Cor treatments on the viability of T24-sensitive and T24/DDPinsensitive bladder carcinoma cells were investigated by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) method to assess selectivity index. Flow cytometry was employed to evaluate the apoptosis of T24/DDP-resistant bladder cancer cells treated with cisplatin and Cor. The concentrations of PTEN, p-AKt and Akt in T24/DDP-resistant bladder cancer cells treated with cisplatin and Cor were determined by western blot assay.Results: Compared with T24-sensitive cells, the sensitivity of T24/DDP-resistant bladder cancer cells to cisplatin was significantly decreased, along with significant increase in half-inhibitory concentration (IC50) value, resulting in 10.56-fold increase in resistance (p < 0.05). The median effective concentration (EC50) value of Cor for DDP reversal was 1.03 ± 0.15 μM, and it had a high selectivity index for normal cells (> 48.5). The results from flow cytometry showed that Cor significantly enhanced the apoptosisinducing capacity of DDP in T24/DDP-resistant cells (p < 0.05), while Western blot data indicate that PTEN protein expression increased and phosphorylated Akt protein expression decreased in T24/DDPresistantcells after Cor treatment when compared with control group (p < 0.05).Conclusion: Cordycepin significantly improves the sensitivity of T24/ DDP-resistant bladder cancer cells to cisplatin via a mechanism related to the activation of PTEN/AKt signaling pathway, thus indicating that it is a potential candidate reversing DDP-resistance in bladder cancer. Keywords: Bladder cancer, Cordycepin, Cisplatin resistance, PTEN/Akt signaling pathway