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Cancer Lett. 2010 Dec 18;299(1):22-8. doi: 10.1016/j.canlet.2010.07.020. Epub 2010 Aug 19.

RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase.

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  • 1Department 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.

PMID:
20727673
[PubMed - indexed for MEDLINE]
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