Open Access

Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil

  • Authors:
    • Shinsuke Sasada
    • Yoshihiro Miyata
    • Yasuhiro Tsutani
    • Naohiro Tsuyama
    • Tsutomu Masujima
    • Jun Hihara
    • Morihito Okada
  • View Affiliations

  • Published online on: December 11, 2012     https://doi.org/10.3892/or.2012.2182
  • Pages: 925-931
  • Copyright: © Sasada et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Metabolomics has developed as an important new tool in cancer research. It is expected to lead to the discovery of biomarker candidates for cancer diagnosis and treatment. The current study aimed to perform a comprehensive metabolomic analysis of the intracellular dynamic responses of human gastric cancer cells to 5-fluorouracil (5-FU), referencing the mechanisms of drug action and drug resistance. Small metabolites in gastric cancer cells and 5-FU-resistant cells were measured by liquid chromatography-mass spectrometry. Candidates for drug targets were selected according to the presence or absence of resistance, before and after 5-FU treatment. In addition, the gene expression of each candidate was assessed by reverse transcription-polymerase chain reaction. The number of metabolites in cancer cells dramatically changed during short-term treatment with 5-FU. Particularly, proline was reduced to one-third of its original level and glutamate was increased by a factor of 3 after 3 h of treatment. The metabolic production of glutamate from proline proceeds by proline dehydrogenase (PRODH), producing superoxide. After 5-FU treatment, PRODH mRNA expression was upregulated 2-fold and production of superoxide was increased by a factor of 3. In 5-FU-resistant cells, proline and glutamate levels were less affected than in non-resistant cells, and PRODH mRNA expression and superoxide generation were not increased following treatment. In conclusion, the authors identified a candidate biomarker, PRODH, for drug effects using a meta­bolomic approach, a result that was confirmed by conventional methods. In the future, metabolomics will play an important role in the field of cancer research.
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March 2013
Volume 29 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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APA
Sasada, S., Miyata, Y., Tsutani, Y., Tsuyama, N., Masujima, T., Hihara, J., & Okada, M. (2013). Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil. Oncology Reports, 29, 925-931. https://doi.org/10.3892/or.2012.2182
MLA
Sasada, S., Miyata, Y., Tsutani, Y., Tsuyama, N., Masujima, T., Hihara, J., Okada, M."Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil". Oncology Reports 29.3 (2013): 925-931.
Chicago
Sasada, S., Miyata, Y., Tsutani, Y., Tsuyama, N., Masujima, T., Hihara, J., Okada, M."Metabolomic analysis of dynamic response and drug resistance of gastric cancer cells to 5-fluorouracil". Oncology Reports 29, no. 3 (2013): 925-931. https://doi.org/10.3892/or.2012.2182