The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells

  • Yi, Hee (College of Veterinary Medicine, Konkuk University) ;
  • Cho, Hee-Jung (College of Veterinary Medicine, Konkuk University) ;
  • Cho, Soo-Min (College of Veterinary Medicine, Konkuk University) ;
  • Jo, Kyul (College of Veterinary Medicine, Konkuk University) ;
  • Park, Jin-A (College of Veterinary Medicine, Konkuk University) ;
  • Lee, Soo-Han (College of Veterinary Medicine, Konkuk University) ;
  • Chang, Byung-Joon (College of Veterinary Medicine, Konkuk University) ;
  • Kim, Jin-Suk (College of Veterinary Medicine, Konkuk University) ;
  • Shin, Ho-Chul (College of Veterinary Medicine, Konkuk University)
  • Received : 2011.09.16
  • Accepted : 2012.01.08
  • Published : 2012.02.29
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Abstract

Cancer stem cells (CSCs) are often characterized by the elevated expression of drug-resistance related stem-cell surface markers, such as CD133 and ABCG2. Recently, we reported that CSCs have a high level of expression of the IL-6 receptor (IL-6R). The purpose of this study was to investigate the effect of anticancer drugs on the expression of the drug resistance-related cancer stem cell markers, ABCG2, IL-6R, and CD133 in non-small cell lung cancer (NSCLC) cell lines. A549, H460, and H23 NSCLC cell lines were treated with the anticancer drugs 5-fluorouracil (5-FU; $25{\mu}g/ml$) and methotrexate (MTX; $50{\mu}g/ml$), and the expression of putative CSC markers was analyzed by fluorescent activated cell sorter (FACS) and the gene expression level of abcg2, il-6r and cd133 by reverse transcriptase-polymerase chain reaction (RT-PCR). We found that the fraction of ABCG2-positive(+) cells was significantly increased by treatment with both 5-FU and MTX in NSCLC cells, and the elevation of abcg2, il-6r and cd133 expressions in response to these drugs was also confirmed using RT-PCR. Also, the number of IL-6R(+) cells was increased by MTX in the 3 cell lines mentioned and increased by 5-FU in the H460 cell line. The number of CD133(+) cells was also significantly increased by both 5-FU and MTX treatment in all of the cell lines tested. These results indicate that 5-FU and MTX considerably enhance the expression of drug-resistance related CSC markers in NSCLC cell lines. Thus, we suggest that antimetabolite cancer drugs, such as 5-FU and MTX, can lead to the propagation of CSCs through altering the expression of CSC markers.

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References

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