Hydroxyurea decreases gemcitabine resistance in pancreatic carcinoma cells with highly expressed ribonucleotide reductase
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Updated: May 29, 2026

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
Published on: November 7, 2019
Naotake Funamizu1, Yuko Kamata, Takeyuki Misawa
1Department of Molecular Cell Biology, Institute of DNA Medicine, The Jikei University School of Medicine, Tokyo, Japan. funamizujikei@yahoo.co.jp
Objectives:
This study aimed to determine whether the treatment of pancreatic carcinoma can be defined on the basis of the expression of genes involved in gemcitabine metabolism and whether combination treatment is more effective than conventional treatment.
Methods:
Four pancreatic carcinoma cell lines (Panc-1, MIAPaCa-2, BxPC-3, and Capan-2) were used to determine the patterns of gemcitabine-metabolizing genes and mesenchymal marker gene expressions using quantitative real-time polymerase chain reaction. Chemosensitivity and cell proliferation were measured using colorimetric assay. Gemcitabine was combined with hydroxyurea or small interfering RNA targeting ribonucleotide reductase to assess changes in chemoresistance.
Results:
Panc-1 and MIAPaCa-2 cell lines were profoundly chemoresistant and expressed genes corresponding to cells with distinct mesenchymal phenotypes. In addition, Panc-1 highly expressed ribonucleotide reductase and showed a 4-fold increase in gemcitabine sensitivity after treatment with hydroxyurea.
Conclusions:
Combination treatment tailored to cells with highly expressed ribonucleotide reductase was more effective than treatment with gemcitabine alone. Moreover, phenotype and gemcitabine metabolism may independently confer chemoresistance.
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