Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

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

Sheng Li, Li-bin Zhou , Tie-lin Wu, Min Yin, Hui-min Long

Department of Urology Surgery, Li Huili Hospital of Ningbo Medical Center, Ningbo City, Zhejiang Province 315000, China; ¹Department of Psychiatry, Xi'an Mental Health Center, Southeast Corner of the Intersection of Aerospace Avenue and Baomao Expressway, Chang'an District, Xi'an City, Shaanxi Province 710061; ²Department of Medical image, Ninth Hospital of Xi’an, no. 151 East Section of South Second Ring, Beilin District, Xi’an City, Shaanxi Province 710054, China;

For correspondence:- Li-bin Zhou Email: m40psz@163.com

Accepted: 25 April 2020 Published: 31 May 2020

Citation: Li S, Zhou L, Wu T, Yin M, Long H. Cordycepin reverses cisplatin resistance in human bladder cancer cells via the PTEN/PI3K/AKt pathway. Trop J Pharm Res 2020; 19(5):965-970 doi: 10.4314/tjpr.v19i5.8

© 2020 The authors.
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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/DDP-insensitive 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 apoptosis-inducing 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/DDP-resistant cells 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