title: HIF-1α siRNA and cisplatin in combination suppress tumor growth in a nude mice model of esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances, and a current challenge is the development of effective therapeutic agents. Our present work addressed the effect of HIF-1α siRNA alone or in combination with cisplatin on the growth of ESCC in nude mice.
  
  
  METHODS
  Xenografts were established by inoculating ESCC TE-1 cells in nude mice, and transplanted tumors were treated with HIF-1α siRNA, cisplatin alone or together. Growth was assessed by measuring tumor volume. HIF-1α mRNA and protein expression were detected using RT-PCR and immunohistochemistry, respectively. Apoptosis of ESCC TE-1 cells was analyzed by flow cytometry.
  
  
  RESULTS
  In our nude mice model, HIF-1α siRNA effectively inhibited the growth of transplanted ESCC, downregulating HIF-1α mRNA and protein expression, and inducing ESCC TE-1 cell apoptosis. Notably when combinated with cisplatin, HIF-1α siRNA showed synergistic interaction in suppressing tumor growth. Furthermore, the proportion of apoptotic cells in HIF- 1α siRNA plus cisplatin group was significantly higher than that in cisplatin or HIF-1α siRNA-treated groups (P<0.05).
  
  
  CONCLUSIONS
  Down-regulated HIF-1α expression induced by siRNA could effectively suppress the growth of transplanted ESCC in vivo. HIF-1α siRNA could enhance the cytotoxicity of cisplatin, which suggests that a combination of these two agents may have potential for therapy of advanced ESCC.
authors.affiliation: Department of Thoracic Surgery, Clinical Research Center of Chest Tumor, the Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Hylmed1996@hotmail.com
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Liao
authors.forename: Gui-Ping
authors.initials: GP
authors.lastname: Wang
authors.forename: Li-Jia
authors.initials: LJ
authors.lastname: Gu
authors.forename: Shao-hong
authors.initials: SH
authors.lastname: Huang
authors.forename: Xiu-Ling
authors.initials: XL
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Li
authors.forename: Song-Wang
authors.initials: SW
authors.lastname: Cai
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D002945:Cisplatin