Bioimpacts of anti epidermal growth factor receptor antisense complexed with polyamidoamine dendrimers in human lung epithelial adenocarcinoma cells.

Abstract

Lung cancer is still one of the leading causes of malignancy related deaths worldwide despite recent advances in diagnosis and therapy. Among various biomarkers detected in cancerous cells, the epidermal growth factor receptor (EGFR) plays a key role in initiation/promotion of several malignancies. Thus, a number of studies have been carried out to target this important receptor. In the present study, effects of anti-EGFR antisense (AS-ODN) nanoparticles formulated with star burst polyamidoamine (PAMAM) dendrimers on the expression of EGFR and its downstream molecules were investigated in human lung cancer A549 cells. Complexation of dendrimers with AS-ODN reduced the zeta potential of nanostructures (approximately 10 mV), but increased their size (approximately150 nm). Fluorescence microscopy revealed high transfection efficiency which was further confirmed with flow cytometry technique. Significant cell growth reduction in the treated cells was detected using MTT assay and marked downregulation of EGFR and some of its downstream signaling biomolecule (i.e., Akt kinase) were observed. Microarray profile revealed nonspecific changes in gene expression in A549 cells upon treatment with PAMAM dendrimers alone or as complexed with As-ODN, while comet assay showed no DNA damage. Based on our findings, EGFR targeting antisense is able to inhibit the growth of A549 cells via downregulation of EGFR and Akt kinase, nevertheless these nanopolyplexes can also induce nonspecific bioimpacts in target cells.