Journal of Shandong University (Health Sciences) ›› 2018, Vol. 56 ›› Issue (3): 41-47.doi: 10.6040/j.issn.1671-7554.0.2017.251

Previous Articles    

Effect of androgen blockade on autophagy and apoptosis in bladder cancer UM-UC-3 cells

HAO Kuiyuan, ZHAO Sheng, ZHANG Yu, CUI Di, JING Yifeng, XIA Shujie, HAN Bangmin   

  1. Department of Urology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai 200080, China
  • Received:2017-03-23 Published:2022-09-27

PDF (PC)

7

Abstract: Objective To explore the effect of androgen ablation and androgen receptor competitor biclutamide on autophagy and apoptosis in bladder cancer UM-UC-3 cells. Methods DHT and bicalutamide were respectively used to activate or inhibit androgen receptor signaling in UM-UC-3 cells. In addition, rapamycin and chloroquine were respectively used to induce or inhibit autophagy in UM-UC-3 cells. Hoechst staining, flow cytometry and Western blotting were used to observe the apoptotis. Autophagy flux was detected and quantified under transmission electronic microscope and confocal fluoresence microscope. Results Elevated autophagy and apoptosis levels were detected in UM-UC-3 cells after androgen ablation and androgen receptor competitor bicalutamide treatment. In addition, apoptosis induced by bicalutamide could be rescued by chloroquine and enhanced by rapamycin. Conclusion Androgen ablation and androgen receptor competitor bicalutamide promote apoptosis in UM-UC-3 cells due to autophagy induction.

Key words: Bladder cancer, Androgen receptor, Bicalutamide, Autophagy, Apoptosis

CLC Number: 

  • R737.14
[1] Torre LA, Bray F, Siegel RL, et al. Global cancer statistics, 2012[J]. CA Cancer J Clin, 2015, 65(2): 87-108.
[2] Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2): 115-132.
[3] Wu JT, Han BM, Yu SQ, et al. Androgen receptor is a potential therapeutic target for bladder cancer[J]. Urology, 2010, 75(4): 820-827.
[4] Jing Y, Cui D, Guo W, et al. Activated androgen receptor promotes bladder cancer metastasis via Slug mediated epithelial-mesenchymal transition[J]. Cancer Lett, 2014, 348(1-2): 135-145.
[5] Shiota M, Takeuchi A, Yokomizo A, et al. Androgen receptor signaling regulates cell growth and vulnerability to Doxorubicin in bladder cancer[J]. J Urol, 2012, 188(1): 276-286.
[6] 崔玉朋, 吴吉涛, 冯帆, 等. 雄激素受体基因对人膀胱癌T24细胞黏附和侵袭力的影响[J]. 中华实验外科杂志, 2013, 30(5): 1007-1009. CUI Yupeng, WU Jitao, FENG Fan, et al. Effects of androgen receptor gene on adhesion and invasion of human bladder cancer T24 cells[J]. Chin J Exp Surg, 2013, 30(5): 1007-1009.
[7] Kawahara T, Ide H, Kashiwagi E, et al. Enzalutamide inhibits androgen receptor-positive bladder cancer cell growth[J]. Urol Oncol, 2016, 34(10): 432.e15-23.
[8] Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation[J]. Science, 2000, 290(5497): 1717-1721.
[9] 殷雷, 殷睿, 李文, 等. CYLD抑制自噬提高膀胱癌细胞吉西他滨化疗敏感性[J].山东大学学报(医学版), 2016, 54(11): 1-6. YIN Lei, YIN Rui, LI Wen, et al. CYLD improves bladder cancer gemcitabine chemosensitivity via suppressing autophagy[J]. Journal of Shandong University(Health Sciences), 2016, 54(11): 1-6.
[10] Li JR, Cheng CL, Yang CR, et al. Dual inhibitor of phosphoinositide 3-kinase/mammalian target of rapamycin NVP-BEZ235 effectively inhibits cisplatin-resistant urothelial cancer cell growth through autophagic flux[J]. Toxicol Lett, 2013, 220(3): 267-276.
[11] Miyamoto H, Yang Z, Chen YT, et al. Promotion of bladder cancer development and progression by androgen receptor signals[J]. J Natl Cancer Inst, 2007, 99(7): 558-568.
[12] Klionsky DJ, Abdelmohsen K, Abe A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy(3rd edition)[J]. Autophagy, 2016, 12(1): 1-222.
[13] Jitao W, Jinchen H, Qingzuo L, et al. Androgen receptor inducing bladder cancer progression by promoting an epithelial-mesenchymal transition[J]. Andrologia, 2014, 46(10): 1128-1133.
[14] Izumi K, Taguri M, Miyamoto H, et al. Androgen deprivation therapy prevents bladder cancer recurrence[J]. Oncotarget, 2014, 5(24): 12665-12674.
[15] Hsu JW, Hsu I, Xu D, et al. Decreased tumorigenesis and mortality from bladder cancer in mice lacking urothelial androgen receptor[J]. Am J Pathol, 2013, 182(5): 1811-1820.
[16] Zhuang YH, Bläuer M, Tammela T, et al. Immunodetection of androgen receptor in human urinary bladder cancer[J]. Histopathology, 1997, 30(6): 556-562.
[17] Mir C, Shariat SF, van der Kwast TH,et al. Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study[J]. BJU Int, 2011, 108(1): 24-30.
[18] Mashhadi R, Pourmand G, Kosari F, et al. Role of steroid hormone receptors in formation and progression of bladder carcinoma: a case-control study[J]. Urol J, 2014, 11(6): 1968-1973.
[19] Bauckman KA, Mysorekar IU. Ferritinophagy drives uropathogenic Escherichia coli persistence in bladder epithelial cells[J]. Autophagy, 2016, 12(5): 850-863.
[20] Mariño G, Nisosantano M, Baehrecke EH, et al. Self-consumption: the interplay of autophagy and apoptosis[J]. Nat Rev Mol Cell Bio, 2014,15(2): 81-94.
[21] Ojha R, Singh SK, Bhattacharyya S, et al. Inhibition of grade dependent autophagy in urothelial carcinoma increases cell death under nutritional limiting condition and potentiates the cytotoxicity of chemotherapeutic agent[J]. J Urol, 2014, 191(6): 1889-1898.
[22] Lin YC, Lin JF, Wen SI, et al. Inhibition of high basal level of autophagy induces apoptosis in human bladder cancer cells[J]. J Urol, 2016, 195(4): 1126-1135.
[23] Huang YT, Cheng CC, Lin TC, et al. Therapeutic potential of sepantronium bromide YM155 in gemcitabine-resistant human urothelial carcinoma cells[J]. Oncol Rep, 2014, 31(2): 771-780.
[24] Zeng LP, Hu ZM, Li K, et al. miR-222 attenuates cisplatin-induced cell death by targeting the PPP2R2A/Akt/mTOR Axis in bladder cancer cells[J]. J Cell Mol Med, 2016, 20(3): 559-567.
[25] Shi Y, Han JJ, Tennakoon JB, et al. Androgens promote prostate cancer cell growth through induction of autophagy[J]. Mol Endocrinol, 2013, 27(2): 280-295.
[26] Boutin B, Tajeddine N, Vandersmissen P, et al. Androgen deprivation and androgen receptor competition by bicalutamide induce autophagy of hormone-resistant prostate cancer cells and confer resistance to apoptosis[J]. Prostate, 2013, 73(10): 1090-1102.
[27] Jiang Q, Yeh S, Wang X, et al. Targeting androgen receptor leads to suppression of prostate cancer via induction of autophagy[J]. J Urol, 2012, 188(4): 1361-1368.
[1] LU Xiang-Dong, YANG Wei, XU Guang-Meng, QU Yuan-Ming. Expression and role of PPAR-γin meningiomas and troglitazone induced meningiomas cell apoptosis in vitro [J]. JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES), 2209, 47(6): 65-.
[2] ZHAO Ge, ZOU Cunhua, SONG Dongdong, ZHAO Shuping. Effects of tanshinone IIA on the proliferation and apoptosis of endometrial carcinoma cells [J]. Journal of Shandong University (Health Sciences), 2022, 60(9): 53-58.
[3] LIU Min, ZHANG Yuchao, MA Xiaoli, LIU Xinyu, SUN Lu, ZUO Dan, LIU Yuantao. Effects of orphan nuclear receptor NR4A1 on H2O2 induced injury of mouse renal podocytes [J]. Journal of Shandong University (Health Sciences), 2022, 60(5): 16-21.
[4] LI Hui, JIANG Chaoyang, LIU Yan, ZHANG Man. Effects and mechanism of histone deacetylase SIRT1 controlled macrophage apoptosis induced by oxidized low density lipoprotein [J]. Journal of Shandong University (Health Sciences), 2022, 60(1): 6-12.
[5] MI Qi, SHI Shuang, LI Juan, LI Peilong, DU Lutao, WANG Chuanxin. Construction of circRNA-mediated ceRNA network and prognostic assessment model for bladder cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 94-102.
[6] XU Bing, LI Yong, LIU Ming, LIU Yonghui. Silencing PRRX1 gene expression enhances the sensitivity of prostate cancer resistant cell line PC-3/DTX to docetaxel [J]. Journal of Shandong University (Health Sciences), 2021, 59(6): 103-110.
[7] LU You, QIE Di, WU Jinhui, YANG Fan. Effects of the intervention of Sonic Hedgehog signaling pathway on learning and memory ability in rats with intrauterine growth restriction [J]. Journal of Shandong University (Health Sciences), 2021, 59(5): 82-89.
[8] ZHANG Xiaohong, ZHOU Yun, DU Qiuying, REN Huixin, WANG Chaoqun. Atg7-siRNA interferes with radiosensitivity of esophageal cancer ECA109 cells by regulating arginine circulation [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 28-34.
[9] NAN Li, YANG Kaizhuan, ZHANG Yifan. Effects of domestic white light-emitting diodes exposure on rat retina [J]. Journal of Shandong University (Health Sciences), 2021, 59(4): 56-62.
[10] LIU Shudan, ZHANG Feiyan, GUO Songlin, LIANG Xueyun, CHEN Dongmei. Oxymatrine ameliorates oxidative stress injury of HaCaT cells induced by hypoxia ischemia [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 26-34.
[11] GAO Jinmei, ZHANG Xianglian, LIU Tieju. Correlation between plasma D-dimer and metastasis in 109 cases of bladder cancer [J]. Journal of Shandong University (Health Sciences), 2021, 59(3): 98-102.
[12] XUE Yuan, LIN Xueyan, XU Ge, TIAN Yongjie. Expression of hypoxia-inducible factor-1α in the serum of patients with endometriosis and its effect on epithelial mesenchymal transition of eutopic endometrial stromal cells [J]. Journal of Shandong University (Health Sciences), 2021, 59(2): 41-47.
[13] LIANG Li, SUN Bin, ZHANG Hongzhan, YE Fangzhi, FENG Xianguang, ZHANG Kai. Analysis of clinical characteristics of 48 cases of gallbladder adenoma based on different pathological grades [J]. Journal of Shandong University (Health Sciences), 2021, 59(1): 59-63.
[14] SUO Dongyang, SHEN Fei, GUO Hao, LIU Lichang, YANG Huimin, YANG Xiangdong. Expression and mechanism of Tim-3 in animal model of drug-induced acute kidney injury [J]. Journal of Shandong University (Health Sciences), 2020, 1(7): 1-6.
[15] ZHANG Xiaolu, WANG Lili, CHEN Kaiming, LOU Xianzhi, ZHANG Man. Mechanism of histone deacetylase SIRT1 inhibiting macrophages apoptosis via TLR4 signaling pathway [J]. Journal of Shandong University (Health Sciences), 2020, 58(12): 8-14.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed   
No Suggested Reading articles found!
Copyright 2018 © Editorial office of Journal of Shandong University (Health Sciences)
Supported by Beijing Magtech Co.Ltd