Silence of fibronectin 1 increases cisplatin sensitivity of non-small cell lung cancer cell line
| Autor: | Weiwei Gao, Ruiling Qin, Ying Liu, Qingqing Feng, Daijian Liu |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Lung Neoplasms Biophysics Antineoplastic Agents Biochemistry 03 medical and health sciences 0302 clinical medicine Cyclin D1 Western blot Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine Humans MTT assay Gene Silencing Protein Interaction Maps Cell adhesion Molecular Biology Lung beta Catenin Cisplatin biology medicine.diagnostic_test Integrin beta1 Wnt signaling pathway Cell Biology Molecular biology Fibronectins Fibronectin Gene Expression Regulation Neoplastic 030104 developmental biology Apoptosis Drug Resistance Neoplasm 030220 oncology & carcinogenesis biology.protein medicine.drug |
| Zdroj: | Biochemical and biophysical research communications. 476(1) |
| ISSN: | 1090-2104 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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