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

  • Authors:
    • Ryuji Ikeda
    • Lee C. Vermeulen
    • Elim Lau
    • Zhisheng Jiang
    • Kamakshi Sachidanandam
    • Katsushi Yamada
    • Jill M. Kolesar
  • View Affiliations

  • Published online on: December 7, 2010     https://doi.org/10.3892/ijo.2010.866
  • Pages: 513-519
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Abstract

Gemcitabine is an effective chemotherapy against non-small cell lung cancer (NSCLC). However, resistance to gemcitabine reduces its efficacy. We have isolated gemcitabine-resistant 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.

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February 2011
Volume 38 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Ikeda R, Vermeulen LC, Lau E, Jiang Z, Sachidanandam K, Yamada K and Kolesar JM: Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells. Int J Oncol 38: 513-519, 2011.
APA
Ikeda, R., Vermeulen, L.C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., & Kolesar, J.M. (2011). Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells. International Journal of Oncology, 38, 513-519. https://doi.org/10.3892/ijo.2010.866
MLA
Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., Kolesar, J. M."Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells". International Journal of Oncology 38.2 (2011): 513-519.
Chicago
Ikeda, R., Vermeulen, L. C., Lau, E., Jiang, Z., Sachidanandam, K., Yamada, K., Kolesar, J. M."Isolation and characterization of gemcitabine-resistant human non-small cell lung cancer A549 cells". International Journal of Oncology 38, no. 2 (2011): 513-519. https://doi.org/10.3892/ijo.2010.866