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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.


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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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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