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Journal of Cancer Research and Clinical Oncology

Published in:

01-12-2010 | Original Paper

Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells

Authors: Hyun Chang, Sun Young Rha, Hei-Cheul Jeung, Jae-Jun Jung, Tae Soo Kim, Ho Jeong Kwon, Byung Soo Kim, Hyun Cheol Chung

Published in: Journal of Cancer Research and Clinical Oncology | Issue 12/2010

Abstract

Purpose

We evaluated the cytotoxic effects of combining suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, with taxanes in human gastric cancer cell lines and assessed the pre-treatment difference of gene expression to identify genes that could potentially mediate the cytotoxic response.

Methods

Gastric cancer cell lines were treated with SAHA and paclitaxel or docetaxel, and the synergistic interaction between the drugs was evaluated in vitro using the combination index (CI) method. We performed significance analysis of microarray (SAM) to identify chemosensitivity-related genes in gastric cancer cell lines that were concomitantly treated with SAHA and taxane. We generated a correlation matrix between gene expression and CI values to identify genes whose expression correlated with a combined effect of taxanes and SAHA.

Results

Combination treatment with taxane and SAHA had a synergistic cytotoxic effect against taxane-resistant gastric cancer cells. We identified 49 chemosensitivity-related genes via SAM analysis. Among them, nine common genes (SLIT2, REEP2, EFEMP2, CDC42SE1, FSD1, POU1F1, ZNF79, ETNK1, and DOCK5) were extracted from the subsequent correlation matrix analysis.

Conclusions

The combination of taxane and SAHA could be efficacious for the treatment of gastric cancer. The genes that were related to the synergistic response to taxane and SAHA could serve as surrogate biomarkers to predict the therapeutic response in gastric cancer patients.

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Title: Identification of genes related to a synergistic effect of taxane and suberoylanilide hydroxamic acid combination treatment in gastric cancer cells
Authors: Hyun Chang
Sun Young Rha
Hei-Cheul Jeung
Jae-Jun Jung
Tae Soo Kim
Ho Jeong Kwon
Byung Soo Kim
Hyun Cheol Chung
Publication date: 01-12-2010
Publisher: Springer-Verlag
Published in: Journal of Cancer Research and Clinical Oncology / Issue 12/2010
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0849-0

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