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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2012 | Research

125I seed irradiation induces up-regulation of the genes associated with apoptosis and cell cycle arrest and inhibits growth of gastric cancer xenografts

Authors: Zhen-Huan Ma, Yong Yang, Lei Zou, Kai-Yuan Luo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2012

Abstract

Background

Iodine 125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. Here, we aim to comprehensively elucidate the biological effects induced by 125I seed irradiation in human gastric cancer xenograft model by using global expression and DNA methylation analyses.

Methods

The 48 mice bearing NCI-N87 gastric cancer xenografts were randomly separated into 2 groups: sham seeds (O mCi) were implanted into the control group (n = 24); 125 l seeds (0.9 mCi) were implanted into the treatment group (n = 24). The mitotic index and apoptotic index were evaluated by quantitative morphometric analysis of the expression of proliferating cell nuclear antigen (PCNA) and in situ terminal transferase-mediated fluorescein deoxy- UTP nick end labeling (TUNEL), respectively. Global gene expression changes induced by 125I seed irradiation were analyzed by using Nimblegen Human gene expression array. DNA methylation profile in the tumors from control group was investigated with methylated DNA immunoprecipitation (MeDIP) and Nimblegen CpG promoter microarrays. The changes in the methylation status of selected genes were further investigated by using MeDIP-PCR.

Results

125I seed irradiation suppresses the growth of gastric cancer xenografts in nude mice. PCNA staining and tissue TUNEL assays showed that both inhibition of cell proliferation and induction of apoptosis contribute to the 125I-induced tumor suppression in nude mouse model. Gene expression profiles revealed that the expression levels of several hundred genes, many of which are associated with apoptosis or cell cycle arrest, including BMF, MAPK8, BNIP3, RFWD3, CDKN2B and WNT9A, were upregulated following 125I seed irradiation. Furthermore, the up-regulation of some of these genes, such as BNIP3 and WNT9A, was found to be associated with irradiation-induced DNA demethylation.

Conclusions

This study revealed that 125I seed irradiation could significantly induce the up-regulation of apoptosis- and cell cycle-related genes in human gastric cancer xenografts. And some of the up-regulation might be attributed to 125I-irradiation induced demethylation in gene promoter regions. Collectively, these findings provided evidence for the efficacy of this modality for the treatment of gastric cancer.

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Title: 125I seed irradiation induces up-regulation of the genes associated with apoptosis and cell cycle arrest and inhibits growth of gastric cancer xenografts
Authors: Zhen-Huan Ma
Yong Yang
Lei Zou
Kai-Yuan Luo
Publication date: 01-12-2012
Publisher: BioMed Central
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2012
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/1756-9966-31-61

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