Cancer Lett. 2010;299(1):22-8.
RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase.
제1저자 이경훈 · 교신저자 방영주,임석아
소속 (1)
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Abstract
We evaluated RAD001, an inhibitor of the mammalian target of rapamycin (mTOR) in human gastric cancer cell lines and determined the molecular mechanisms. RAD001 has marked growth inhibitory activity against the SNU-1 and SNU-216 cells. It inhibited phosphorylation of mTOR and S6K, and induced G1 cell cycle arrest. Synergistic growth-inhibitory effects in combination with 5-fluorouracil (5-FU) was identified. Furthermore, RAD001 conferred sensitivity to 5-FU-resistant cell lines by downregulating thymidylate synthase (TS). In conclusion, RAD001 showed growth inhibitory activity against gastric cancer cells and acted synergistically with cytotoxic agents such as 5-FU by downregulating TS.
Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
그 밖의 정보
- 출판 형태
- Journal Article, Research Support, Non-U.S. Gov't
- 저널
- Cancer letters · eISSN 1872-7980
- 전자 출판
- 2010-08-19
- MeSH
- Cell Line, Tumor · Cell Proliferation / drug effects · Drug Resistance, Neoplasm · Everolimus · Fluorouracil / pharmacology · G1 Phase / drug effects · Humans · Intracellular Signaling Peptides and Proteins / antagonists & inhibitors · Protein Serine-Threonine Kinases / antagonists & inhibitors · Sirolimus / analogs & derivatives / pharmacology · Stomach Neoplasms / drug therapy / pathology · TOR Serine-Threonine Kinases · Thymidylate Synthase / antagonists & inhibitors / genetics
- Substances
- Intracellular Signaling Peptides and Proteins · Everolimus · Thymidylate Synthase · MTOR protein, human · Protein Serine-Threonine Kinases · TOR Serine-Threonine Kinases · Fluorouracil · Sirolimus