PMID- 20727673
OWN - NLM
STAT- MEDLINE
DCOM- 20101102
LR  - 20211203
IS  - 1872-7980 (Electronic)
IS  - 0304-3835 (Linking)
VI  - 299
IP  - 1
DP  - 2010 Dec 18
TI  - RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance 
      by downregulating thymidylate synthase.
PG  - 22-8
LID - 10.1016/j.canlet.2010.07.020 [doi]
AB  - 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.
CI  - Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.
FAU - Lee, Kyung-Hun
AU  - Lee KH
AD  - Department of Internal Medicine, Seoul National University College of Medicine, 
      Seoul, Republic of Korea.
FAU - Hur, Hyung-Seok
AU  - Hur HS
FAU - Im, Seock-Ah
AU  - Im SA
FAU - Lee, Juhee
AU  - Lee J
FAU - Kim, Hwang-Phill
AU  - Kim HP
FAU - Yoon, Young-Kwang
AU  - Yoon YK
FAU - Han, Sae-Won
AU  - Han SW
FAU - Song, Sang-Hyun
AU  - Song SH
FAU - Oh, Do-Youn
AU  - Oh DY
FAU - Kim, Tae-You
AU  - Kim TY
FAU - Bang, Yung-Jue
AU  - Bang YJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100819
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 9HW64Q8G6G (Everolimus)
RN  - EC 2.1.1.45 (Thymidylate Synthase)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - U3P01618RT (Fluorouracil)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Drug Resistance, Neoplasm
MH  - Everolimus
MH  - Fluorouracil/*pharmacology
MH  - G1 Phase/drug effects
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*antagonists & inhibitors
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - Sirolimus/*analogs & derivatives/pharmacology
MH  - Stomach Neoplasms/*drug therapy/pathology
MH  - TOR Serine-Threonine Kinases
MH  - Thymidylate Synthase/*antagonists & inhibitors/genetics
EDAT- 2010/08/24 06:00
MHDA- 2010/11/03 06:00
CRDT- 2010/08/24 06:00
PHST- 2010/02/19 00:00 [received]
PHST- 2010/06/22 00:00 [revised]
PHST- 2010/07/22 00:00 [accepted]
PHST- 2010/08/24 06:00 [entrez]
PHST- 2010/08/24 06:00 [pubmed]
PHST- 2010/11/03 06:00 [medline]
AID - S0304-3835(10)00379-4 [pii]
AID - 10.1016/j.canlet.2010.07.020 [doi]
PST - ppublish
SO  - Cancer Lett. 2010 Dec 18;299(1):22-8. doi: 10.1016/j.canlet.2010.07.020. Epub 
      2010 Aug 19.