Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells.
10.4196/kjpp.2012.16.1.11
- Author:
Hee YI
1
;
Hee Jung CHO
;
Soo Min CHO
;
Kyul JO
;
Jin A PARK
;
Soo Han LEE
;
Byung Joon CHANG
;
Jin Suk KIM
;
Ho Chul SHIN
Author Information
1. College of Veterinary Medicine, Konkuk University, Seoul 143-701, Korea. hshin@konkuk.ac.kr
- Publication Type:Original Article
- Keywords:
Cancer stem cell;
5-FU/MTX;
ABCG2/IL-6R/CD133;
Drug resistance
- MeSH:
Carcinoma, Non-Small-Cell Lung;
Cell Line;
Drug Resistance;
Fluorouracil;
Gene Expression;
Methotrexate;
Neoplastic Stem Cells;
Receptors, Interleukin-6
- From:The Korean Journal of Physiology and Pharmacology
2012;16(1):11-16
- CountryRepublic of Korea
- Language:English
-
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 microg/ml) and methotrexate (MTX; 50 microg/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.
