| RRC ID |
66084
|
| 著者 |
Ishida K, Ito C, Ohmori Y, Kume K, Sato KA, Koizumi Y, Konta A, Iwaya T, Nukatsuka M, Kobunai T, Takechi T, Nishizuka SS.
|
| タイトル |
Inhibition of PI3K suppresses propagation of drug-tolerant cancer cell subpopulations enriched by 5-fluorouracil.
|
| ジャーナル |
Sci Rep
|
| Abstract |
Drug-tolerant cancer cell subpopulations are responsible for relapse after chemotherapy. By continuously exposing the gastric cancer cell line MKN45 to 5-FU for >100 passages, we established a 5-fluorouracil (5-FU)-tolerant line, MKN45/5FU. Orthotopic xenografts of MKN45/5FU cells in the stomach of nude mice revealed that these cells had a high potential to metastasize to sites such as the liver. Levels of phosphorylated phosphatidylinositide 3-kinase (PI3K) increased both in 5-FU-tolerant subpopulations according to the 5-FU dose, and in gastric submucosal orthotopic xenografts of MKN45/5FU cells. Sequential administration of 5-FU and a PI3K inhibitor, GDC-0941, targeted the downstream ribosomal S6 kinase phosphorylation to significantly suppress 5-FU-tolerant subpopulations and tumor propagation of orthotopic MKN45/5FU xenografts. These results suggest that administration of 5-FU followed by GDC-0941 may suppress disease relapse after 5-FU-based gastric cancer chemotherapy.
|
| 巻・号 |
7(1)
|
| ページ |
2262
|
| 公開日 |
2017-5-23
|
| DOI |
10.1038/s41598-017-02548-9
|
| PII |
10.1038/s41598-017-02548-9
|
| PMID |
28536445
|
| PMC |
PMC5442158
|
| MeSH |
Animals
Antimetabolites, Antineoplastic / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Class I Phosphatidylinositol 3-Kinases / antagonists & inhibitors
Class I Phosphatidylinositol 3-Kinases / genetics
Class I Phosphatidylinositol 3-Kinases / metabolism
Codon
Disease Models, Animal
Dose-Response Relationship, Drug
Drug Resistance, Neoplasm / drug effects*
Drug Resistance, Neoplasm / genetics
Fluorouracil / pharmacology*
Genetic Variation
Heterografts
Humans
Mice
Neoplasms / genetics
Neoplasms / metabolism
Neoplasms / pathology
Phenotype
Phosphatidylinositol 3-Kinases / genetics
Phosphatidylinositol 3-Kinases / metabolism
Phosphoinositide-3 Kinase Inhibitors*
Phosphorylation
Proteome
Proteomics / methods
Ribosomal Protein S6 Kinases, 90-kDa / metabolism
Signal Transduction
|
| IF |
3.998
|
| リソース情報 |
| ヒト・動物細胞 |
MKN45(RCB1001)
MKN74(RCB1002) |
