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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 
Citation
 JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY, Vol.136(12) : 1901-1913, 2010 
Journal Title
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
ISSN
 0171-5216 
Issue Date
2010
MeSH
Algorithms ; Animals ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents/pharmacology ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival ; Cluster Analysis ; Dose-Response Relationship, Drug ; Drug Synergism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hydroxamic Acids/administration & dosage ; Hydroxamic Acids/pharmacology* ; Inhibitory Concentration 50 ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/genetics ; Stomach Neoplasms/pathology ; Taxoids/administration & dosage ; Taxoids/pharmacology* ; Xenograft Model Antitumor Assays
Keywords
Suberoylanilide hydroxamic acid ; Taxane ; Combination chemotherapy ; Chemosensitivity ; Biological marker ; Stomach neoplasms
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.
Full Text
http://link.springer.com/article/10.1007%2Fs00432-010-0849-0
DOI
10.1007/s00432-010-0849-0
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Rha, Sun Young(라선영) ORCID logo https://orcid.org/0000-0002-2512-4531
Chang, Hyun(장현)
Chung, Hyun Cheol(정현철) ORCID logo https://orcid.org/0000-0002-0920-9471
Jeung, Hei Cheul(정희철) ORCID logo https://orcid.org/0000-0003-0952-3679
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/101080
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