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学科主题: 临床医学
题名:
Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways
作者: Gai, Jun-Wei1,2; Wahafu, Wasilijiang3; Hsieh, Ya-Ching4; Liu, Miao5; Zhang, Liang6; Li, Sheng-Wen7; Zhang, Bei1,2; He, Qun1,2; Guo, Hui7; Jin, Jie1,2
关键词: Urothelial cell carcinoma of the urinary bladder ; Bladder cancer ; Presenilin ; gamma-Secretase ; DAPT
刊名: UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS
发表日期: 2014
DOI: 10.1016/j.urolonc.2013.02.014
卷: 32, 期:1
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology ; Urology & Nephrology
研究领域[WOS]: Oncology ; Urology & Nephrology
关键词[WOS]: ENDOTHELIAL GROWTH-FACTOR ; GAMMA-SECRETASE ; FACTOR VEGF ; EXPRESSION ; CARCINOMA ; TUMORS ; THERAPIES ; DISEASE ; FAMILY ; LINES
英文摘要:

Objective: Presenilin (PS)/gamma-secretase is a key protease that initiates various biological processes. We investigated the effect of PS/gamma-secretase on the expression and inhibition of umthelial cell carcinoma of bladder (UCB) as a potential alternative therapeutic target for UCB.

Materials and methods: PS-1 and PS-2 were identified in normal and malignant human bladder transitional cells by immunohistochemistry. We blocked PSs using a PS/gamma-secretase inhibitor N-(N-[3,5-difluorophenacetyl]-L-alanyl)-S-phenylglycine-t-butylester (DAPT), and the proliferative and invasive potential of UCB cells SW780, BIU-87, 5637, and T24, and human normal urothelial cell line SV-HUC-1 were analyzed using Western blot, cell viability test, flow cytometry, and transwell assay. All experiments were repeated at least 3 times.

Results: Human bladder samples of UCB, SW780, BIU-87, 5637, and T24 cells expressed higher PS-1 compared with normal ones. Cell vitality test demonstrated that DAPT attenuated UCB cell proliferation more than SV-HUC-1. Flow cytometry and transwell assay showed that T24 cells were arrested at G1/S checkpoint and its invasive ability was impaired. Western blot assay markedly showed that protein levels of CD44-intracellular domain, insulinlike growth factor-IR beta, extracellular regulated protein kinase 1/2, cyclin D1, proliferating cell nuclear antigen, and matrix metalloproteinase-9 were downregulated by DAPT, whereas vascular endothelial growth factor receptor-2 and vascular endothelial growth factor-165 were upregulated.

Conclusions: Our study revealed that PS-1 might be implicated in the proliferation and invasion of UCB. and that it may serve as a potential therapeutic target for UCB, but further studies are warranted to verify the effects of inhibition of PS/gamma-secretase on angiogenesis. (C) 2014 Elsevier Inc. All rights reserved.

语种: 英语
所属项目编号: 30571851 ; 81201527
项目资助者: National Natural Science Foundation of China
WOS记录号: WOS:000347243300051
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/52310
Appears in Collections:北京大学第一临床医学院_泌尿外科_期刊论文

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作者单位: 1.Peking Univ, Hosp 1, Dept Urol, Beijing 100871, Peoples R China
2.Peking Univ, Inst Urol, Beijing 100871, Peoples R China
3.China PLA Gen Hosp, Dept Urol, Beijing, Peoples R China
4.Peking Univ, Hosp 1, Dept Anesthesiol & Intens Care, Beijing 100871, Peoples R China
5.HeDong Ctr Dis Control & Prevent, Tianjin, Peoples R China
6.Peking Univ, Clin Coll 4, Beijing Jishuitan Hosp, Dept Orthopaed Surg, Beijing 100871, Peoples R China
7.Tsinghua Univ, Hosp 1, Dept Urol, Beijing 100084, Peoples R China

Recommended Citation:
Gai, Jun-Wei,Wahafu, Wasilijiang,Hsieh, Ya-Ching,et al. Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways[J]. UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS,2014,32(1).
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