title: RAD001 shows activity against gastric cancer cells and overcomes 5-FU resistance by downregulating thymidylate synthase.
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.
authors: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
authors: Kyung-Hun
authors: KH
authors: Lee
authors: Hyung-Seok
authors: HS
authors: Hur
authors: Seock-Ah
authors: SA
authors: Im
authors: Juhee
authors: J
authors: Lee
authors: Hwang-Phill
authors: HP
authors: Kim
authors: Young-Kwang
authors: YK
authors: Yoon
authors: Sae-Won
authors: SW
authors: Han
authors: Sang-Hyun
authors: SH
authors: Song
authors: Do-Youn
authors: DY
authors: Oh
authors: Tae-You
authors: TY
authors: Kim
authors: Yung-Jue
authors: YJ
authors: Bang
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm; D000068338:Everolimus; D005472:Fluorouracil / Q000494:pharmacology*; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D058570:TOR Serine-Threonine Kinases; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D000068338:Everolimus; D013940:Thymidylate Synthase; C546842:MTOR protein, human; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D005472:Fluorouracil; D020123:Sirolimus