抄録
Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+ cells were then measured. CD44+CD133+ DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+ DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+ DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+ DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.
| 元の言語 | 英語 |
|---|---|
| 記事番号 | 14861 |
| ジャーナル | Scientific reports |
| 巻 | 9 |
| 発行部数 | 1 |
| DOI | |
| 出版物ステータス | 出版済み - 12 1 2019 |
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All Science Journal Classification (ASJC) codes
- General
これを引用
CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure. / Tsunekuni, Kenta; Konno, Masamitsu; Haraguchi, Naotsugu; Koseki, Jun; Asai, Ayumu; Matsuoka, Kazuaki; Kobunai, Takashi; Takechi, Teiji; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi.
：: Scientific reports, 巻 9, 番号 1, 14861, 01.12.2019.研究成果: ジャーナルへの寄稿 › 記事
}
TY - JOUR
T1 - CD44/CD133-Positive Colorectal Cancer Stem Cells are Sensitive to Trifluridine Exposure
AU - Tsunekuni, Kenta
AU - Konno, Masamitsu
AU - Haraguchi, Naotsugu
AU - Koseki, Jun
AU - Asai, Ayumu
AU - Matsuoka, Kazuaki
AU - Kobunai, Takashi
AU - Takechi, Teiji
AU - Doki, Yuichiro
AU - Mori, Masaki
AU - Ishii, Hideshi
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+ cells were then measured. CD44+CD133+ DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+ DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+ DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+ DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.
AB - Cancer stem cells (CSCs) are involved in metastatic colorectal cancer recurrence, but no effective therapy targeting these cells is currently available. Because trifluridine (FTD)/tipiracil therapy is used for refractory colorectal cancer, we sought to determine whether FTD is effective against CSC-like cells. CD44+CD133+ high-expressing and other populations of human DLD-1 colon cancer cells were separately isolated through fluorescence-activated cell sorting. The sphere-forming activity of each population and the anti-sphere-forming effects of FTD and fluorouracil (5-FU) on CD44+CD133+ cells were then measured. CD44+CD133+ DLD-1 cells formed substantially more spheres than other cells. Moreover, treating CD44+CD133+ DLD-1 cells with subtoxic concentrations of FTD (1 µM) inhibited sphere formation, and this was superior to the effect of subtoxic concentrations (1 µM) of 5-FU. The associated inhibition rates for FTD and 5-FU were 58.2% and 26.1%, respectively. Further, CD44+CD133+ DLD-1 cells expressed higher levels of thymidine kinase 1, which is responsible for FTD phosphorylation, than DLD-1 cells, and FTD was incorporated into the DNA of CD44+CD133+ DLD-1 cells. Thus, our data show that FTD treatment is effective against CSC-like cells and might be applied as CSC-targeting chemotherapy for tumor subtypes with high CD44 and CD133 expression.
UR - http://www.scopus.com/inward/record.url?scp=85073446365&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073446365&partnerID=8YFLogxK
U2 - 10.1038/s41598-019-50968-6
DO - 10.1038/s41598-019-50968-6
M3 - Article
C2 - 31619711
AN - SCOPUS:85073446365
VL - 9
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
IS - 1
M1 - 14861
ER -