title: Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells.
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 µg/ml) and methotrexate (MTX; 50 µg/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 transcriptasepolymerase 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.
authors.affiliation: College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea.
authors.forename: Hee
authors.initials: H
authors.lastname: Yi
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Cho
authors.forename: Soo-Min
authors.initials: SM
authors.lastname: Cho
authors.forename: Kyul
authors.initials: K
authors.lastname: Jo
authors.forename: Jin-A
authors.initials: JA
authors.lastname: Park
authors.forename: Soo-Han
authors.initials: SH
authors.lastname: Lee
authors.forename: Byung-Joon
authors.initials: BJ
authors.lastname: Chang
authors.forename: Jin-Suk
authors.initials: JS
authors.lastname: Kim
authors.forename: Ho-Chul
authors.initials: HC
authors.lastname: Shin