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

被引：26
作者：
Chang, Hyun [1 ,2 ]
Rha, Sun Young [1 ,2 ,3 ]
Jeung, Hei-Cheul [1 ,2 ]
Jung, Jae-Jun [2 ,3 ]
Kim, Tae Soo [2 ]
Kwon, Ho Jeong [4 ]
Kim, Byung Soo [2 ]
Chung, Hyun Cheol [1 ,2 ,3 ]
机构：
[1] Yonsei Univ, Coll Med, Yonsei Canc Ctr, Div Med Oncol,Dept Internal Med, Seoul 120752, South Korea
[2] Yonsei Univ, Canc Metastasis Res Ctr, Seoul 120752, South Korea
[3] Yonsei Univ, Brain Korea Project Med Sci 21, Seoul 120752, South Korea
[4] Yonsei Univ, Coll Engn, Dept Biotechnol, Chem Genom Lab, Seoul 120752, South Korea
来源：
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY | 2010年 / 136卷 / 12期
关键词：
Suberoylanilide hydroxamic acid; Taxane; Combination chemotherapy; Chemosensitivity; Biological marker; Stomach neoplasms; HISTONE DEACETYLASE INHIBITORS; HDAC INHIBITORS; OVARIAN-CANCER; LUNG-CANCER; PHASE-II; EXPRESSION; GROWTH; ADENOCARCINOMA; CHEMOTHERAPY; PACLITAXEL;
D O I：
10.1007/s00432-010-0849-0
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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. 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. 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. 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.
引用
收藏
页码：1901 / 1913
页数：13
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