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

• Published in: Journal of cancer research and clinical oncology Vol. 136; no. 12; pp. 1901 - 1913
• Main Authors: Chang, Hyun, Rha, Sun Young, Jeung, Hei-Cheul, Jung, Jae-Jun, Kim, Tae Soo, Kwon, Ho Jeong, Kim, Byung Soo, Chung, Hyun Cheol
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Berlin/Heidelberg : Springer-Verlag 01.12.2010; Springer-Verlag; Springer; Springer Nature B.V
• Subjects: Algorithms; Animals; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - pharmacology; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biological marker; Biomarkers; Cancer; Cancer Research; Cell Line; Cell Line, Tumor; Cell Proliferation - drug effects; Cell Survival; Chemosensitivity; Chemotherapy; Clinical outcomes; Cluster Analysis; Combination chemotherapy; Dose-Response Relationship, Drug; Drug Synergism; Female; Gastroenterology. Liver. Pancreas. Abdomen; Gastrointestinal diseases; Gene expression; Gene Expression Profiling; Gene Expression Regulation, Neoplastic - drug effects; Hematology; Humans; Hydroxamic Acids - administration & dosage; Hydroxamic Acids - pharmacology; Inhibitory Concentration 50; Internal Medicine; Medical sciences; Medicine; Medicine & Public Health; Mice; Mice, Inbred BALB C; Mice, Nude; Oncology; Original Paper; Pharmacology. Drug treatments; stomach neoplasms; Stomach Neoplasms - drug therapy; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Suberoylanilide hydroxamic acid; Taxane; Taxoids - administration & dosage; Taxoids - pharmacology; Tumors; Xenograft Model Antitumor Assays; Chemosensitivity; Biological marker; Taxane; Combination chemotherapy; Suberoylanilide hydroxamic acid; Stomach neoplasms; Drug combination; Hydroxamic acid; Identification; Malignant tumor; Stomach cancer; Gene; Taxane derivatives; Digestive diseases; Genetics; Combined treatment; Tumor cell; Cancer; Gastric disease
• ISSN: 0171-5216; 1432-1335
• DOI: 10.1007/s00432-010-0849-0

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.