title: Down-regulation of platelet-derived growth factor-D expression blockades NF-κB pathway to inhibit cell proliferation and invasion as well as induce apoptosis in esophageal squamous cell carcinoma.
abstract: Substantial evidence has demonstrated that platelet-derived growth factor-D (PDGF-D) is tightly associated with the development and progression of tumors. However, its biological functions in esophageal squamous cell carcinoma (ESCC) remain to be delineated. In this study, we found that expressions of PDGF-D mRNA and protein in ESCC tissues and cells were significantly higher than that in normal esophageal epithelial tissues (P < 0.05), further investigation showed that PDGF-D protein level in EC1 cells was obviously higher than those in EC9706 and Eca109 cells (P < 0.05). Elevated PDGF-D level was closely associated with TNM staging, tumor differentiation and lymph node metastasis (P < 0.05), but not related to the patients' age and gender (P > 0.05). In addition, down-regulation of PDGF-D expression markedly inhibited proliferation, reduced invasion and induced apoptosis in EC1 cells. More importantly, reduced PDGF-D level evoked the down-regulation of p65 and p-IκBα proteins and elevation of IκBα protein of NF-κB pathway, accompanied with the decreases of bcl-2 and MMP-9 protein expressions and increases of bax protein level and caspase-3 activities. Correctively, our data suggest that PDGF-D plays pivotal roles in the development and progression of ESCC, and combinations with PDGF-D and NF-κB pathway may be effective and feasible molecular targets for therapy of ESCC.
authors.affiliation: Department of Gastroenterology, The First Affiliated Hospital of Xinxiang Medical University, No. 88 Health Road, Weihui, 453100, Henan Province, People's Republic of China. hyxxm2012@126.com
authors.forename: Yu
authors.initials: Y
authors.lastname: Han
authors.forename: Xiao-He
authors.initials: XH
authors.lastname: Guo
authors.forename: Qing-Fen
authors.initials: QF
authors.lastname: Zheng
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Zhu
authors.forename: Ying-Ying
authors.initials: YY
authors.lastname: Fan
authors.forename: Xiu-Ying
authors.initials: XY
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D004947:Esophagus; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008222:Lymphokines / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009092:Mucous Membrane / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D008222:Lymphokines; D016328:NF-kappa B; C427493:PDGFD protein, human; D010982:Platelet-Derived Growth Factor; D012333:RNA, Messenger; D053148:Caspase 3