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Vol. 88, No. 1, 2012
Issue release date: January 2012
Section title: Original Paper
Urol Int 2012;88:95–101
(DOI:10.1159/000331881)

Effects of YC-1 on Hypoxia-Inducible Factor 1 Alpha in Hypoxic Human Bladder Transitional Carcinoma Cell Line T24 Cells

Li Y. · Zhao X. · Tang H. · Zhong Z. · Zhang L. · Xu R. · Li S. · Wang Y.
aDepartment of Urology, Second Xiangya Hospital, Central South University, Changsha, and bSchool of Nursing, Fudan University, Shanghai, China

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Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/22/2011 11:12:57 AM
Accepted: 8/1/2011
Published online: 10/25/2011

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN

Abstract

Objectives: It was the aim of this study to explore the effects of 3-(5′-hydroxymethyl-2′-furyl)-l-benzyl indazole (YC-1) on transcription activity, cell proliferation and apoptosis of hypoxic human bladder transitional carcinoma cells (BTCC), mediated by hypoxia-inducible factor 1α (HIF-1α). Methods: BTCC cell line T24 cells were incubated under normoxic or hypoxic conditions, adding different doses of YC-1. The protein expression of HIF-1α and HIF-1α-mediated genes was detected by Western blotting. RT-PCR was used to detect HIF-1α mRNA expression. Cell proliferation, apoptosis and migration activity were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and transwell migration assay. The cells were pretreated by two ERK/p38 MAPK pathway-specific inhibitors, PD98059 or SB203580, and then incubated with YC-1 treatment under hypoxic condition. HIF-1α protein expression was detected by Western blotting. Results: Hypoxic T24 cells expressed a higher level of HIF-1α, vascular endothelial growth factor, matrix metalloproteinases-2, B-cell lymphoma/leukemia-2 protein and HIF-1α mRNA compared with normoxic controls, in which the above-mentioned expression was downregulated by YC-1 in a dose-dependent manner. Cell proliferation and migration activity were inhibited while apoptosis was induced by YC-1 under hypoxic condition. Moreover, YC-1-downregulated HIF-1α expression was reversed by PD98059 and SB203580, respectively. Conclusions: YC-1 inhibits HIF-1α and HIF-1α-mediated gene expression, cell proliferation and migration activity and induces apoptosis in hypoxic BTCC. The ERK/p38 MAPK pathway may be involved in YC-1-mediated inhibition of HIF-1α.


  

Author Contacts

Xiaokun Zhao, MD
Department of Urology, Second Xiangya Hospital
Central South University
Changsha, Hunan 410011 (China)
Tel. +86 13 574 896 469, E-Mail zhaoxiaokun60@163.com

  

Article Information

Received: March 22, 2011
Accepted after revision: August 1, 2011
Published online: October 25, 2011
Number of Print Pages : 7
Number of Figures : 4, Number of Tables : 0, Number of References : 28

  

Publication Details

Urologia Internationalis

Vol. 88, No. 1, Year 2012 (Cover Date: January 2012)

Journal Editor: Wirth M.P. (Dresden), Porena M. (Perugia), Hakenberg O.W. (Rostock), Castro-Diaz D. (Santa Cruz de Tenerife)
ISSN: 0042-1138 (Print), eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: 3/22/2011 11:12:57 AM
Accepted: 8/1/2011
Published online: 10/25/2011

Number of Print Pages: 7
Number of Figures: 4
Number of Tables: 0

ISSN: 0042-1138 (Print)
eISSN: 1423-0399 (Online)

For additional information: http://www.karger.com/UIN


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