論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | MKN45(RCB1001) MKN74(RCB1002) |