title: Knockdown of S100A7 reduces lung squamous cell carcinoma cell growth in vitro and in vivo.
abstract: OBJECTIVE
  S100A7 plays a role in the malignant potential of several epithelial cancers, and could candidate diagnostic marker or therapeutic target. Nuclear factor kappa B (NF-κB) regulates cancer cell growth and is modulated by phospholipase activity in many cancer cells. In the present study, we first evaluate the involvement of S100A7 in lung squamous cell carcinoma and its clinical usefulness for diagnosis. We then study whether knockdown of S100A7 in lung squamous cell carcinoma cells would reduce cell proliferation and NF-κB activity in vitro and attenuate tumor growth in vivo.
  
  
  METHODS
  We examined S100A7 expression in lung squamous cell carcinoma tissues by immunohistology .The human lung squamous cell carcinoma cell line NCI-H520 were transduced with short hairpin RNA targeting S100A7. Quantitative reverse transcriptase-polymerase chain reaction and immunoblotting confirmed knockdown of S100A7 messenger RNA and protein, respectively. Cell proliferation was evaluated by the MTT assay. NF-κB phosphorylation was assayed by western blot. 1×10(6) of NCI-H520/S100A7 knockdown cells were injected into the left flanks of nude mice (aged 6 to 8 weeks). Tumors were followed for 35 days, then removed and stained with hematoxylin and eosin, stained with Ki-67, and analyzed for S100A7 protein expression.
  
  
  RESULTS
  S100A7 protein levels were significantly higher in carcinoma specimens than in nonneoplastic tissues. S100A7 might be a useful marker for diagnosis of lung squamous cell carcinoma. In vitro data showed that inhibition of S100A7 decreased proliferation of NCI-H520 cells. S100A7 knockdown reduced NF-κB phosphorylation and tumor growth in vivo and vivo. Explanted knockdown tumors maintained lower S100A7 levels compared with wild-type, confirmed by immunohistology. Ki-67 staining was more prominent throughout the wild-type tumors compared with knockdown tumors.
  
  
  CONCLUSIONS
  Our present results suggest that S100A7 level is a promising tool for diagnosis of lung squamous cell carcinoma. Knockdown of S100A7 suppresses lung cancer growth in part by attenuating NF-κB activity. S100A7 may be a promising therapeutic target for lung squamous cell carcinoma.
authors.affiliation: Department of Cytology Laboratory, People's Hospital of Linyi Shandong, 276300, China.
authors.forename: Guijuan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Clinical Laboratory, People's Hospital of Linyi Shandong, 276300, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Nursing, People's Hospital of Linyi Shandong, 276300, China.
authors.forename: Guilan
authors.initials: G
authors.lastname: Liu
authors.affiliation: Department of Thoracic Surgery, The People's Hospital of Rizhao Rizhao, China.
authors.forename: Xueying
authors.initials: X
authors.lastname: Song
authors.affiliation: Department of Clinical Laboratory, People's Hospital of Linyi Shandong, 276300, China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D016328:NF-kappa B; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human
keywords: Lung squamous cell carcinoma; NF-κB; S100A7