title: Inhibition of hypoxia inducible factor 1α expression suppresses the progression of esophageal squamous cell carcinoma.
abstract: Hypoxia inducible factor 1α (HIF-1α) is highly expressed and is implicated in the progression of esophageal squamous cell carcinoma. To investigate the potential mechanism by which HIF-1α contributes to the progression of esophageal squamous cell carcinoma, here we established stable esophageal carcinoma cell lines Eca-109 and TE- 13 in which HIF-1α was depleted by shRNA mediated gene silencing. In additon, we used specific inhibitor YC-1 to inhibit HIF-1α expression. Our in vitro studies demonstrated that shRNA or chemical mediated inhibition of HIF-1α led to reduced proliferation and increased apoptosis of esophageal carcinoma cells, as well as the downregulatuion of HIF-1α targets VEGF, MMP2 and BCL2. Furthermore, we employed xenograft nude mice model to validate the in vitro findings and proved that depletion of HIF-1α suppressed the tumorigenicity of esophageal carcinoma cells in vivo. In conclusion, our results provide new insight into the potential role of HIF-1α in esophageal squamous cell carcinoma and open up the possibility of inhibiting HIF-1α for targeted therapy of esophageal squamous cell carcinoma.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhu
authors.forename: Yadong
authors.initials: Y
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiqiao
authors.initials: X
authors.lastname: Zhou
authors.forename: Bo
authors.initials: B
authors.lastname: Hao
authors.forename: Guoxin
authors.initials: G
authors.lastname: Zhang
authors.forename: Ruihua
authors.initials: R
authors.lastname: Shi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D015687:Cell Hypoxia / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D007191:Indazoles / Q000494:pharmacology; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007191:Indazoles; C090937:3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole