title: EGFR antisense oligonucleotides encapsulated with nanoparticles decrease EGFR, MAPK1 and STAT5 expression in a human colon cancer cell line.
abstract: Epidermal growth factor receptor (EGFR) is over-expressed in several human cancers. This would suggest that inhibition of EGFR is a reasonable approach for cancer treatment. In this study we investigated EGFR blocking and its effects on the mediated signaling such as MAPK and STATb in HT29 cells. For this aim we used FITC-labeled EGFR antisense oligonucleotides encapsulated with PAMAM nanoparticles to inhibit EGFR expression. Cellular uptake of antisense was investigated by fluorescence microscopy and flow cytometry analysis. The effect of EGFR antisense on the expression of EGFR in HT29 cells was examined by real time PCR and Western blots, which showed that antisense encapsulated with PAMAM decreased the level of EGFR mRNA and protein. In addition, real time PCR results confirmed that EGFR inhibition had an effective role in the reduction of EGFR dependent downstream genes. In conclusion, EGFR antisense encapsulated with PAMAM nanoparticles down regulated EGFR and EGFR-mediated genes.
authors.affiliation: Department of Biochemistry and Kerman Physiology Research Center, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran.
authors.forename: Ahmad Gholamhoseinian
authors.initials: AG
authors.lastname: Najar
authors.forename: Roghiyeh
authors.initials: R
authors.lastname: Pashaei-Asl
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Omidi
authors.forename: Safar
authors.initials: S
authors.lastname: Farajnia
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Nourazarian
mesh_terms: D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019073:HT29 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics*; D053758:Nanoparticles; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C512478:EGFR protein, human; D066246:ErbB Receptors; D019950:Mitogen-Activated Protein Kinase 1