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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/43108
Title: Haem oxygenase 1 expression is associated with prognosis in cholangiocarcinoma patients and with drug sensitivity in xenografted mice
Authors: S. Kongpetch
A. Puapairoj
C. K. Ong
L. Senggunprai
A. Prawan
U. Kukongviriyapan
W. Chan-On
E. Y. Siew
N. Khuntikeo
B. T. Teh
V. Kukongviriyapan
Khon Kaen University
National Cancer Centre, Singapore
National University of Singapore
Cancer Science Institute of Singapore
Mahidol University
Keywords: Biochemistry, Genetics and Molecular Biology
Issue Date: 1-Feb-2016
Citation: Cell Proliferation. Vol.49, No.1 (2016), 90-101
Abstract: © 2016 John Wiley & Sons Ltd. Objective: Haem oxygenase-1 (HO-1) plays important roles in cytoprotection and tumour growth. Cholangiocarcinoma (CCA) is a deadly malignancy with very poor prognosis. The role of HO-1 in tumour progression in CCA up to now has been relatively unexplored, thus, its possible therapeutic implications in CCA have been investigated here. Materials and methods: HO-1 expression in tumour tissues from 50 CCA patients was determined by immunohistochemical analysis and its association with survival time was evaluated using the Kaplan-Meier method. Its role in CCA cells in vitro was evaluated by transwell and wound healing assays and suppression of HO-1 expression by siRNA. Effects of HO-1 inhibition on gemicitabine (GEM)-mediated tumour suppression was evaluated in nude mice xenografted with CCA cells. Results: HO-1 expression was inversely associated with median overall survival time. Hazard ratio of patients with high HO-1 expression was 2.42 (95% CI: 1.16-5.08) with reference to low expression and HO-1 knock-down expression inhibited transwell cell migration. Suppression of HO-1 by Zn-protoporphyrin (ZnPP) enhanced cytotoxicity to GEM in CCA cells, validated in CCA xenografts. Treatment with GEM and ZnPP almost completely arrested tumour growth, whereas treatment with only a single reagent, retarded it. Tumour inhibition was associated with reduction in expression of Ki-67 and microvascular density, and enhanced p53 and p21 immunohistochemical staining. Conclusion: High HO-1 expression was associated with poor prognosis of CCA. Synergistic role of HO-1 inhibition in chemotherapy of CCA is a promising insight for treatment of this tumour and warrants further investigation.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84958866770&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/43108
ISSN: 13652184
09607722
Appears in Collections:Scopus 2016-2017

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