Modulation of membrane properties of lung cancer cells by azurin enhances the sensitivity to EGFR-targeted therapy and decreased 1 integrin-mediated adhesion

被引:32
作者
Bernardes, Nuno [1 ]
Abreu, Sofia [1 ]
Carvalho, Filomena A. [2 ]
Fernandes, Fabio [3 ]
Santos, Nuno C. [2 ]
Fialho, Arsenio M. [1 ,4 ]
机构
[1] iBB Inst Bioengn & Biosci, Biol Sci Res Grp, Lisbon, Portugal
[2] Univ Lisbon, Fac Med, Inst Mol Med, Lisbon, Portugal
[3] Inst Super Tecn, Ctr Quim Fis Mol, Lisbon, Portugal
[4] Univ Lisbon, Inst Super Tecn, Dept Bioengn, Lisbon, Portugal
关键词
atomic force microscoy; azurin; EGFR; gefitinib; NSCLC; (1); integrin; REDOX PROTEIN AZURIN; HUMAN BREAST-CANCER; PEPTIDE INHIBITOR; DRUG-RESISTANCE; GEFITINIB; BINDING; GROWTH; SPECIFICITY; LAMININ-5; CARCINOMA;
D O I
10.1080/15384101.2016.1172147
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
In lung cancer, the Epidermal Growth Factor Receptor (EGFR) is one of the main targets for clinical management of this disease. The effectiveness of therapies toward this receptor has already been linked to the expression of integrin receptor subunit (1) in NSCLC A549 cells. In this work we demonstrate that azurin, an anticancer therapeutic protein originated from bacterial cells, controls the levels of integrin (1) and its appropriate membrane localization, impairing the intracellular signaling cascades downstream these receptors and the invasiveness of cells. We show evidences that azurin when combined with gefitinib and erlotinib, tyrosine kinase inhibitors which targets specifically the EGFR, enhances the sensitivity of these lung cancer cells to these molecules. The broad effect of azurin at the cell surface level was examined by Atomic Force Microscopy. The Young 's module (E) shows that the stiffness of A549 lung cancer cells decreased with exposure to azurin and also gefitinib, suggesting that the alterations in the membrane properties may be the basis of the broad anticancer activity of this protein. Overall, these results show that azurin may be relevant as an adjuvant to improve the effects of other anticancer agents already in clinical use, to which patients often develop resistance hampering its full therapeutic response
引用
收藏
页码:1415 / 1424
页数:10
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