Overcoming doxorubicin resistance of cancer cells by Cas9-mediated gene disruption

• DOI: 10.1038/srep22847
• Publication Date: 2016-03-10T10:39:56Z
• Authors: Jong Seong Ha; Juyoung Byun; Dae-Ro Ahn
• Keywords: 0303 health sciences; Antibiotics, Antineoplastic; RNA, Guide, CRISPR-Cas Systems; Transfection; Article; Drug Resistance, Multiple; 3. Good health; 03 medical and health sciences; Doxorubicin; Drug Resistance, Neoplasm; MCF-7 Cells; Mutagenesis, Site-Directed; Humans; Clustered Regularly Interspaced Short Palindromic Repeats; ATP Binding Cassette Transporter, Subfamily B, Member 1; CRISPR-Cas Systems; Plasmids

Abstract In this study, Cas9 system was employed to down-regulate mdr1 gene for overcoming multidrug resistance of cancer cells. Disruption the MDR1 achieved by delivery Cas9-sgRNA plasmid or ribonucleoprotein complex using a conventional transfection agent and protein transduction domain (PTD). Doxorubicin showed considerable cytotoxicity drug-resistant breast cells pre-treated with RNA-guided endonuclease (RGEN) systems, whereas virtually non-toxic untreated The potency drug enhanced in treated protein-RNA as well those plasmids, suggesting that mutation intracellular proper platforms could recover susceptibility. Therefore, Cas9-mediated disruption resistance-related can be considered promising way overcome