title: Silence of fibronectin 1 increases cisplatin sensitivity of non-small cell lung cancer cell line.
abstract: Fibronectin 1 (FN1) is a member of the glycoprotein family which is widely expressed by multiple cell types and involved in cellular adhesion and migration processes. Recent studies have reported that FN1 might have a role in regulating chemoresistance in tumors. However, the regulation of FN1 on cisplatin resistance in non-small cell lung cancer (NSCLC) has not been investigated. The present study aims to illustrate the effect of FN1 on cisplatin resistance in NSCLC and explore potential mechanisms. In the present study, the mRNA and protein expression levels of FN1 were investigated by RT-PCR and Western blot analysis, respectively, and the 50% inhibitory concentration (IC50) value of cisplatin was measured by MTT assay. Apoptotic ratio and migration were determined using an annexin V-FITC/PI detection kit and a Transwell assay, respectively. The interaction between FN1 and integrin-β1 was evaluated by co-immunoprecipitation assay. The protein expression of β-catenin, cyclin D1 and c-myc were tested using Western blot analysis. The results showed that FN1 was more highly expressed in A549/DDP than in A549 cells, and significantly upregulated by cisplatin treatment in H1299 cells. Knockdown of FN1 reduced the IC50 value of cisplatin, inhibited cell migration and promoted apoptosis. FN1 and integrin-β1 protein directly interacted with each other both in A549 and A549/DDP cells. FN1 silencing suppressed the Wnt/β-catenin signaling pathway, and this effect was dampened by integrin-β1-blocking antibody. Taken together, our findings first suggest that FN1 plays a role in the development of cisplatin resistance in NSCLC, possibly by modulation of β-catenin signaling through interaction with integrin-β1 in NSCLC.
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou, 450014, PR China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou, 450014, PR China. Electronic address: yingliusec@163.com.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou, 450014, PR China.
authors.forename: Ruiling
authors.initials: R
authors.lastname: Qin
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou, 450014, PR China.
authors.forename: Daijian
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Respiratory Medicine, The Second Affiliated Hospital of Zhengzhou University, ZhengZhou, 450014, PR China.
authors.forename: Qingqing
authors.initials: Q
authors.lastname: Feng
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D005353:Fibronectins / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D060066:Protein Interaction Maps; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C067625:FN1 protein, human; D005353:Fibronectins; D019012:Integrin beta1; D051176:beta Catenin; D002945:Cisplatin
keywords: Apoptosis; Cisplatin resistance; Fibronectin 1; Migration; Non-small cell lung cancer