Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells

Ryuji Ikeda, Lee C. Vermeulen, Elim Lau, Zhisheng Jiang, Kamakshi Sachidanandam, Katsushi Yamada, Jill M. Kolesar

Research output: Contribution to journalArticlepeer-review

27 Scopus citations


Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabineresistant human non-small cell lung cancer A549 cells, termed A549/GR cells. A549/GR cells were resistant to gemcitabine as well as paclitaxel and docetaxel but not carboplatin and irinotecan. The expression level of multidrug resistance protein 7 (MRP7) in A549/GR cells was higher than that in A549 cells, and the inhibitor of MRP7 by cepharanthine increased the sensitivity to gemcitabine in A549/GR cells. These findings indicate that cepharanthine reversed gemcitabine resistance. To determine predictive molecular markers of gemcitabine resistance for more effective treatment of these tumors, we performed PCR array. We identified that CDKN1A/p21, CYP3A5, microsomal epoxide hyrolase 1 (EPHX1) and ABCC6 (MRP6) were up-regulated >5-fold in A549/GR cells. Gemcitabine also induced the expression of p21 and CYP3A5 in A549 cells. A better understanding of the characterization and mechanism of the resistance to gemcitabine in A549/GR cells may help identify agents that reverse clinical gemcitabine resistance in NSCLC.

Original languageEnglish
Pages (from-to)513-519
Number of pages7
JournalInternational Journal of Oncology
Issue number2
StatePublished - Feb 2011


  • A549 cells
  • Gemcitabine
  • Non-small cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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