Androgen receptor antagonist bicalutamide induces autophagy and apoptosis via ULK2 upregulation in human bladder cancer cells.

Studies have demonstrated a close link between autophagy and bladder cancer. The androgen receptor (AR) has also been found to be closely involved in bladder cancer progression. Although androgen ablation and AR antagonism have been proposed as potential methods for bladder cancer therapy, the mechanisms underlying their effects remain poorly understood. This study was designed to assess the effects of the AR antagonist bicalutamide on autophagy and apoptosis in bladder cancer cells. The results indicated that the AR has an inhibitory effect on autophagy in bladder cancer cells. Using different tests, we observed that bicalutamide promotes apoptosis in these cells and positively modulates autophagy in UM-UC-3 cells by upregulating ULK2. In addition, ULK2 knockdown inhibited autophagy and apoptosis in bladder cancer cells. Autophagy promotion by rapamycin enhanced apoptosis in bladder cancer cells, especially in AR-positive UM-UC-3 cells when AR signaling was inhibited by bicalutamide. These findings suggest that the AR antagonist bicalutamide induces autophagy and apoptosis in bladder cancer cells and may have potential in bladder cancer therapy because it upregulates autophagic flux by targeting the AR and its downstream gene ULK2.

International journal of clinical and experimental pathology. 2017 Jul 01*** epublish ***

Kuiyuan Hao, Sheng Zhao, Di Cui, Yu Zhang, Chenyi Jiang, Yifeng Jing, Shujie Xia, Bangmin Han

Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine Shanghai, China.