RRC ID 45430
著者 Liu G, Wu Q, Liu G, Song X, Zhang J.
タイトル Knockdown of S100A7 reduces lung squamous cell carcinoma cell growth in vitro and in vivo.
ジャーナル Int J Clin Exp Pathol
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.
巻・号 7(11)
ページ 8279-89
公開日 2014-1-1
PMID 25550886
PMC PMC4270552
MeSH Adult Aged Aged, 80 and over Animals Biomarkers, Tumor / analysis Blotting, Western Carcinoma, Squamous Cell / mortality Carcinoma, Squamous Cell / pathology* Cell Proliferation Female Gene Knockdown Techniques Heterografts Humans Immunohistochemistry In Vitro Techniques Kaplan-Meier Estimate Lung Neoplasms / mortality Lung Neoplasms / pathology* Male Mice Mice, Nude Middle Aged NF-kappa B Prognosis Real-Time Polymerase Chain Reaction Reverse Transcriptase Polymerase Chain Reaction S100 Calcium Binding Protein A7 S100 Proteins / metabolism*
IF 0.252
引用数 7
WOS 分野 PATHOLOGY ONCOLOGY
リソース情報
ヒト・動物細胞 LC-2/ad(RCB0440)