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Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma

  • Original article
  • Published:
Journal of Hepato-Biliary-Pancreatic Sciences

Abstract

Background

Gemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes.

Methods

Expressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis.

Results

p53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC50 > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway.

Conclusions

Increased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.

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Acknowledgments

We would like to express our immense gratitude to Ms. Yuka Kimura and Ms. Hidemi I for their technical assistance.

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Authors and Affiliations

  1. Department of Organ Regenerative Surgery, Fukushima Medical University, 1 Hikarigaoka, Fukushima, 960-1295, Japan

    Jun Sato, Takashi Kimura, Takuro Saito, Takayuki Anazawa, Akira Kenjo, Yoshihiro Sato, Takao Tsuchiya & Mitsukazu Gotoh

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  1. Jun Sato
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  2. Takashi Kimura
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  3. Takuro Saito
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  4. Takayuki Anazawa
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  5. Akira Kenjo
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  6. Yoshihiro Sato
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  7. Takao Tsuchiya
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  8. Mitsukazu Gotoh
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Correspondence to Takashi Kimura.

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Sato, J., Kimura, T., Saito, T. et al. Gene expression analysis for predicting gemcitabine resistance in human cholangiocarcinoma. J Hepatobiliary Pancreat Sci 18, 700–711 (2011). https://doi.org/10.1007/s00534-011-0376-7

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  • DOI: https://doi.org/10.1007/s00534-011-0376-7

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