Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines

  • Authors:
    • Masanori Shimomura
    • Takeshi Yaoi
    • Kyoko Itoh
    • Daishiro Kato
    • Kunihiko  Terauchi
    • Junichi Shimada
    • Shinji Fushiki
  • View Affiliations

  • Published online on: December 13, 2011     https://doi.org/10.3892/ijo.2011.1297
  • Pages: 995-1004
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Abstract

In order to clarify the mechanisms of resistance to paclitaxel in lung cancer, three human lung cancer cell lines which exhibit different sensitivity to paclitaxel were investigated from the following viewpoints: overexpression of ATP-binding cassette, sub-family B, member 1 (ABCB1), mutations on paclitaxel binding site of β-tubulin genes, quantity of polymerized tubulin and the intracellular localization of paclitaxel. ABCB1 expression was evaluated by real-time RT-PCR. No correlations were noted between the ABCB1 expression in the sensitive and resistant cell lines at the mRNA level. No mutations on the paclitaxel binding site of the β-tubulin genes were detected in either the resistant or sensitive cells. Live cell images obtained by confocal laser microscopy revealed that the resistant cell line, RERF-LC-KJ, had more accumulation of Oregon Green® 488 conjugated paclitaxel in the lysosomal and extra-lysosomal compartments of cytoplasm than other cell lines. The results obtained in this study indicated that the changes in the subcellular localization could contribute to the production of paclitaxel resistance in lung cancer cell lines. Further studies should be conducted to elucidate the molecular mechanisms that differentiate the intracellular localization of paclitaxel.
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April 2012
Volume 40 Issue 4

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Spandidos Publications style
Shimomura M, Yaoi T, Itoh K, Kato D, Terauchi K, Shimada J and Fushiki S: Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines. Int J Oncol 40: 995-1004, 2012
APA
Shimomura, M., Yaoi, T., Itoh, K., Kato, D., Terauchi, K., Shimada, J., & Fushiki, S. (2012). Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines. International Journal of Oncology, 40, 995-1004. https://doi.org/10.3892/ijo.2011.1297
MLA
Shimomura, M., Yaoi, T., Itoh, K., Kato, D., Terauchi, K., Shimada, J., Fushiki, S."Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines". International Journal of Oncology 40.4 (2012): 995-1004.
Chicago
Shimomura, M., Yaoi, T., Itoh, K., Kato, D., Terauchi, K., Shimada, J., Fushiki, S."Drug resistance to paclitaxel is not only associated with ABCB1 mRNA expression but also with drug accumulation in intracellular compartments in human lung cancer cell lines". International Journal of Oncology 40, no. 4 (2012): 995-1004. https://doi.org/10.3892/ijo.2011.1297