Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells

• 영문명: Effect of 5-FU and MTX on the Expression of Drug-resistance Related Cancer Stem Cell Markers in Non-small Cell Lung Cancer Cells
• 발행기관: 대한생리학회-대한약리학회
• 저자명: Hee Yi Hee-Jung Cho Soo-Min Cho Kyul Jo Jin-A Park Soo-Han Lee Byung-Joon Chang Jin-Suk Kim Ho-Chul
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제16권 제1호, 11~16쪽, 전체 6쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2012.01.01

영문 초록

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 Ռg/ml) and methotrexate (MTX; 50 Ռg/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.

키워드

Cancer stem cell 5-FU/MTX ABCG2/IL-6R/CD133 Drug resistance