您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2018, Vol. 56 ›› Issue (3): 41-47.doi: 10.6040/j.issn.1671-7554.0.2017.251

• • 上一篇    

雄激素阻断对膀胱癌UM-UC-3细胞自噬与凋亡的影响

蒿魁元,赵圣,张宇,崔迪,荆翌峰,夏术阶,韩邦旻   

  1. 上海交通大学附属第一人民医院泌尿外科, 上海 200080
  • 收稿日期:2017-03-23 发布日期:2022-09-27
  • 通讯作者: 韩邦旻. E-mail:hanbm@163.com
  • 基金资助:
    国家自然科学基金(81372754)

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

摘要: 目的 探讨雄激素阻断对膀胱癌UM-UC-3细胞自噬与凋亡的影响。 方法 以双氢睾酮或比卡鲁胺激活或抑制UM-UC-3细胞AR信号通路,以雷帕霉素或氯喹进一步诱导或抑制UM-UC-3细胞自噬水平,根据以上不同处理条件进行相应分组。采用Hoechst染色、流式细胞仪和Western blotting检测UM-UC-3细胞凋亡;采用透射电镜、激光共聚焦显微镜和Western blotting检测UM-UC-3细胞自噬水平。 结果 雄激素去除或者AR阻断剂比卡鲁胺可以增强膀胱癌UM-UC-3细胞自噬和凋亡水平;雄激素阻断对UM-UC-3细胞的凋亡促进作用可以被氯喹抑制,并且可以被雷帕霉素增强。 结论 雄激素去除和AR阻断剂比卡鲁胺可以促进UM-UC-3细胞凋亡,这与其诱导细胞发生自噬相关。

关键词: 膀胱癌, 雄激素受体, 比卡鲁胺, 自噬, 凋亡

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

中图分类号: 

  • 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] 张士宝 刘庆勇 阮喜云 陈杰 张建军 李宗武 杨广笑 王全颖. NT4-SAC-HA2-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[2] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[3] 赵舸,邹存华,宋冬冬,赵淑萍. 丹参酮IIA对子宫内膜癌细胞增殖与凋亡的影响[J]. 山东大学学报 (医学版), 2022, 60(9): 53-58.
[4] 刘敏,张玉超,马小莉,刘昕宇,孙露,左丹,刘元涛. 孤核受体NR4A1在H2O2诱导小鼠肾脏足细胞损伤中的作用[J]. 山东大学学报 (医学版), 2022, 60(5): 16-21.
[5] 李卉,姜朝阳,刘岩,张曼. 组蛋白去乙酰化酶SIRT1调控氧化低密度脂蛋白诱导巨噬细胞凋亡的表达[J]. 山东大学学报 (医学版), 2022, 60(1): 6-12.
[6] 米琦,史爽,李娟,李培龙,杜鲁涛,王传新. 膀胱癌circRNAs介导的ceRNA网络及预后评估模型的构建[J]. 山东大学学报 (医学版), 2021, 59(6): 94-102.
[7] 徐兵,李勇,刘明,刘永辉. 沉默PRRX1基因表达可增强前列腺癌耐药细胞株PC-3/DTX对多西他赛的敏感性[J]. 山东大学学报 (医学版), 2021, 59(6): 103-110.
[8] 卢游,且迪,伍晋辉,杨凡. 干预Sonic Hedgehog信号通路对宫内发育迟缓新生大鼠学习记忆能力的影响[J]. 山东大学学报 (医学版), 2021, 59(5): 82-89.
[9] 张华宇,殷思源,刘健,马嘉旭,宋茹,曹国起,王一兵. 氧糖剥夺条件下培养表皮干细胞的定量蛋白质组学分析[J]. 山东大学学报 (医学版), 2021, 59(4): 17-27.
[10] 张小红,周云,杜秋莹,任慧欣,王超群. Atg7-siRNA通过调节精氨酸循环干扰食管癌ECA109细胞放疗敏感性[J]. 山东大学学报 (医学版), 2021, 59(4): 28-34.
[11] 南莉,杨凯转,张一帆. 室内照明白色发光二极管对大鼠视网膜的影响[J]. 山东大学学报 (医学版), 2021, 59(4): 56-62.
[12] 刘淑丹,张飞燕,郭松林,梁雪云,陈冬梅. 氧化苦参碱改善缺氧缺血引起的HaCaT细胞氧化应激损伤[J]. 山东大学学报 (医学版), 2021, 59(3): 26-34.
[13] 薛源,林雪艳,徐歌,田永杰. 低氧诱导因子-1α在子宫内膜异位症患者血清中的表达和对在位子宫内膜间质细胞上皮-间质转化的影响[J]. 山东大学学报 (医学版), 2021, 59(2): 41-47.
[14] 索东阳,申飞,郭皓,刘力畅,杨惠敏,杨向东. Tim-3在药物性急性肾损伤动物模型中的表达及作用机制[J]. 山东大学学报 (医学版), 2020, 1(7): 1-6.
[15] 张晓璐,王丽莉,陈凯明,娄宪芝,张曼. 组蛋白去乙酰化酶SIRT1经Toll样受体4途径对巨噬细胞凋亡的调控[J]. 山东大学学报 (医学版), 2020, 58(12): 8-14.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!