Journal of Cancer Research and Clinical Oncology

, Volume 136, Issue 12, pp 1901–1913 | Cite as

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

  • Hyun Chang
  • Sun Young Rha
  • Hei-Cheul Jeung
  • Jae-Jun Jung
  • Tae Soo Kim
  • Ho Jeong Kwon
  • Byung Soo Kim
  • Hyun Cheol Chung
Original Paper

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.

Keywords

Suberoylanilide hydroxamic acid Taxane Combination chemotherapy Chemosensitivity Biological marker Stomach neoplasms 

Notes

Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MOST) (R11-2000-082-03002-0)

Conflict of interest statement

We declare that we have no conflict of interest.

Supplementary material

432_2010_849_MOESM1_ESM.doc (28 kb)
Online Resource 1 (a) Dose-dependent growth inhibition by SAHA in human gastric cancer cell lines for 72 h. (b) Comparison of the IC50 of SAHA in human gastric cancer cell lines (■) and non-malignant human cell lines (□) (DOC 27 kb)
432_2010_849_MOESM2_ESM.tif (165 kb)
Online Resource 2 The growth of the human gastric cancer xenograft in nude mice treated with SAHA (10 μM and 20 μM). *: p value corresponding to the difference between the control group and the 20 μM SAHA group; p=0.009 at day seven, p=0.016 at day nine, and p=0.016 at day 14. The p values were calculated by the Wilcoxon signed ranks test. The bars represent the standard error of the surviving animals in each group (TIFF 164 kb)
432_2010_849_MOESM3_ESM.tif (643 kb)
Online Resource 3 Combination indices at the IC50 level for 25 human gastric cancer cell lines treated with SAHA and paclitaxel (a), SAHA and docetaxel (b), as calculated by the method previously described by Chou and Talalay (TIFF 643 kb)
432_2010_849_MOESM4_ESM.pdf (36 kb)
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432_2010_849_MOESM5_ESM.pdf (7 kb)
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432_2010_849_MOESM6_ESM.pdf (75 kb)
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432_2010_849_MOESM7_ESM.pdf (76 kb)
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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Hyun Chang
    • 1
    • 2
  • Sun Young Rha
    • 1
    • 2
    • 3
  • Hei-Cheul Jeung
    • 1
    • 2
  • Jae-Jun Jung
    • 2
    • 3
  • Tae Soo Kim
    • 2
  • Ho Jeong Kwon
    • 4
  • Byung Soo Kim
    • 2
  • Hyun Cheol Chung
    • 1
    • 2
    • 3
  1. 1.Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer CenterYonsei University College of MedicineSeoulKorea
  2. 2.Cancer Metastasis Research CenterYonsei UniversitySeoulKorea
  3. 3.Brain Korea 21 Project for Medical ScienceYonsei UniversitySeoulKorea
  4. 4.Chemical Genomics Laboratory, Department of Biotechnology, College of EngineeringYonsei UniversitySeoulKorea

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