title: [Combined inhibition of STAT3 and HIF-1α for enhancement of chemosensitivity in the model of human laryngeal squamous cacinoma in nude mice].
abstract: OBJECTIVE
  To investigate the effects of combined inhibition of signal transducer and activator of transcription 3 (STAT3) and hypoxia-inducible factor-1α (HIF-1α) in the enhancement of chemosensitivity of the model of human laryngeal squamous cacinoma in nude mice.
  
  
  METHODS
  Model nude mice were divided into six groups randomly: control group(A) , cisplatin group(B) , cisplatin and AG490 group(C) , cisplatin and HIF-1α⁻/⁻ group (D), cisplatin combined AG490 and HIF-1α⁻/⁻ group (E), HIF-1α⁻/⁻ group (F) (only in calculating tumor inhibition rate). 3mg/kg cisplatin was administered by peritoneal injection for 3 days. Then cisplatin and 10 mg/kg AG490 were administered every other day for 12 days. The expression of Ki67 and HIF-1α was detected by immunocytochemical method. Western blot was used to detect the expression of p-STAT3.
  
  
  RESULTS
  The expression of HIF-1α in group C and group D were lower than that in group B, and there were significant difference respectively (t₁ = 2.782, t₂ = 3.873, P < 0.05); The expression of HIF-1α in group E was lower than that in group C and group D respectively, and there were significant difference respectively (t₁ = 6.140, t₂ = 3.667, P < 0.01). The expression level of p-STAT3 in group C was markedly lower compared with that in group B, and there were significant difference between them (t = 17.840, P < 0.01); There were no difference between the expression level of p-STAT3 in group D and that in group B (t = 0.038, P > 0.05); The expression level of p-STAT3 in group E was significantly lower compared with that in group C and group D respectively (P < 0.01). Tumor inhibition rate of group E was higher than that in group B, group C , as well as group D respectively and there were significant difference respectively (t₁ = 5.509, P < 0.01; t₂ = 3.422, P < 0.05; t₃ = 2.718, P < 0.05 ). Ki67 index of group E was lower than that in group B, group C as well as group D respectively and there were significant difference respectively(t₁ = 8.307, P < 0.01; t₂ = 3.736, P < 0.05; t₃ = 4.524, P < 0.01).
  
  
  CONCLUSIONS
  Combined inhibition of STAT3 and HIF-1α could enhance chemo-sensitivity in the model of human laryngeal squamous cacinoma in nude mice.
authors.forename: Xiuying
authors.initials: X
authors.lastname: Lu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Song
authors.forename: Xiuru
authors.initials: X
authors.lastname: Ma
authors.forename: Lifeng
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D019394:Ki-67 Antigen / Q000378:metabolism; D007822:Laryngeal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D002945:Cisplatin