IR@PKUHSC  > 北京大学第一临床医学院  > 泌尿外科
学科主题临床医学
Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways
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
2014
DOI10.1016/j.urolonc.2013.02.014
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
WOS记录号WOS:000347243300051
项目编号30571851 ; 81201527
资助机构National Natural Science Foundation of China
引用统计
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/52310
专题北京大学第一临床医学院_泌尿外科
北京大学第三临床医学院_麻醉科
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
推荐引用方式
GB/T 7714
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).
APA Gai, Jun-Wei.,Wahafu, Wasilijiang.,Hsieh, Ya-Ching.,Liu, Miao.,Zhang, Liang.,...&Jin, Jie.(2014).Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways.UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS,32(1).
MLA Gai, Jun-Wei,et al."Inhibition of presenilins attenuates proliferation and invasion in bladder cancer cells through multiple pathways".UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS 32.1(2014).
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