Combined EGFR and c-Src Antisense Oligodeoxynucleotides Encapsulated with PAMAM Denderimers Inhibit HT-29 Colon Cancer Cell Proliferation

Nourazarian, Ali Reza; Najar, Ahmad Gholamhoseinian; Farajnia, Safar; Khosroushahi, Ahmad Yari; Pashaei-Asl, Roghiyeh; Omidi, Yadollah

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저자정보: Nourazarian, Ali Reza (Department of Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences) Najar, Ahmad Gholamhoseinian (Biochemistry Department and Kerman Physiology Research Center, Kerman University of Medical Sciences) Farajnia, Safar (Drug Applied Research Center & Biotechnology Research Center, Tabriz University of Medical Sciences) Khosroushahi, Ahmad Yari (Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences) Pashaei-Asl, Roghiyeh (Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences) Omidi, Yadollah (Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences)

저널정보: 아시아태평양암예방학회 Asian Pacific journal of cancer prevention : APJCP Asian Pacific journal of cancer prevention : APJCP 제13권 제9호

발행연도: 2012.1

수록면: 4,751 - 4,756 (6page)

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Colon cancer continues to be one of the most common cancers, and the importance and necessity of new therapies needs to be stressed. The most important proto-oncogen factors for colon cancer appear to be epidermal growth factor receptor, EGFR, and c-Src with high expression and activity leading to tumor growth and ultimately to colon cancer progression. Application of c-Src and EGFR antisense agents simultaneously should theoretically therefore have major benefit. In the present study, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were combined in a formulation using PAMAM dendrimers as a carrier. Nano drug entry into cells was confirmed by flow cytometry and fluorescence microscopy imaging and real time PCR showed gene expression of c-Src and EGFR, as well as downstream STAT5 and MAPK-1 with the tumor suppressor gene P53 to all be downregulated. EGFR and c-Src protein expression was also reduced when assessed by western blotting techniques. The effect of the antisense oligonucleotide on HT29 cell proliferation was determined by MTT assay, reduction beijng observed after 48 hours. In summary, nano-drug, anti-EGFR and c-Src specific antisense oligodeoxynucleotides were effectively transferred into HT-29 cells and inhibited gene expression in target cells. Based on the results of this study it appears that the use of antisense EGFR and c-Src simultaneously might have a significant effect on colon cancer growth by down regulation of EGFR and its downstream genes.

#Colon cancer #HT-29 #antisense #EGFR #c-Src #PAMAM dendrimers

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Nourazarian, Ali Reza

소속기관 Research Center for Pharmaceutical Nanotechnology, Faculty of Medicine, Tabriz University of Medical