title: Mechanistic target of rapamycin small interfering RNA and rapamycin synergistically inhibit tumour growth in a mouse xenograft model of human oesophageal carcinoma.
abstract: OBJECTIVE
  To investigate the effect of mechanistic target of rapamycin (mTOR)-specific small interfering RNA (siRNA) and rapamycin on tumour size and levels of hypoxia inducible factor 1α(HIF-1α), vascular endothelial growth factor (VEGF) and mTOR proteins, and mTOR mRNA, in a mouse xenograft model of human oesophageal carcinoma.
  
  
  METHODS
  Tumours were induced in BALB/c nude mice using the human oesophageal squamous cell carcinoma cell line, EC1, injected subcutaneously. Animals were divided into four treatment groups (n = 5 per group) after 7 days: control (phosphate buffered saline, daily intraperitoneal [i.p.] injection); 50 μg/kg rapamycin, daily i.p. injection; 3 μg/kg mTOR siRNA, daily i.p. injection; combined mTOR siRNA and rapamycin, daily i.p. injections. Tumour volume was measured 21 days after xenograft. Levels of mTOR, VEGF and HIF-1α were assessed via immunohistochemistry and in situ hybridization.
  
  
  RESULTS
  mTOR siRNA and/or rapamycin significantly decreased tumour volume and levels of HIF-1α, VEGF and mTOR protein, and mTOR mRNA. Combination treatment was significantly more effective than either treatment alone.
  
  
  CONCLUSIONS
  mTOR siRNA and/or rapamycin inhibited the growth of oesophageal carcinoma in vivo. This may represent a novel and effective treatment strategy for oesophageal carcinoma.
authors.affiliation: Department of Oncology, First Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: M M
authors.initials: MM
authors.lastname: Sun
authors.forename: M Z
authors.initials: MZ
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: S L
authors.initials: SL
authors.lastname: Li
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.forename: G W
authors.initials: GW
authors.lastname: Ya
authors.forename: K S
authors.initials: KS
authors.lastname: Chen
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004938:Esophageal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D034741:RNA, Small Interfering / Q000235:genetics; D020123:Sirolimus / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000903:Antibiotics, Antineoplastic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus