A STAT3-Decoy Oligodeoxynucleotide Suppresses Cell Growth and Induces Apoptosis in Erlotinib Resistant SW480 Colon Cancer Cell Line by Blockage of the STAT3 Signaling Pathway

Background and Aim: Colon cancer persists as one of the most prevalentand deadly tumor types worldwide. The emergence of resistance tochemotherapy is a major clinical problem. STAT3 (signal transducer andactivator of transcription 3) is frequently activated in tumor cells andplays a prominent role in proliferation, chemotherapy-resistance. Thepresent study was to test the hypothesis that inhibition of STAT3 decreasegrowth and induce apoptosis in Erlotinib resistant SW480 colon cancercell line.Methods: First, sense and antisense sequence of decoy and scrambleoligodeoxynucleotide for STAT3 transcription factor designed based onSTAT3 elements in the promoter region of the MYCT1 gene. To confirmspecific binding of the STAT3 nuclear proteins with STAT3 decoy ODNsEMSA dual protein-nucleic acid staining Kit was used. Fluorescentmicroscopy was done to determine the subcellular localization oflabeled decoys. Investigation of cell viability, apoptosis and expressionlevel of downstream genes in SW480 cells carried out by MTT, Annexinv/pi test and Real-time PCR assay, respectively.Results: EMSA indicate that specific binding between STAT3 decoy toSTAT3 protein in nuclear extract of SW480 cells. Transfection of STAT3ODNs potently represses erlotinib-resistant colon cancer cell line inassociation with reducing cell viability reduction, apoptosis promotionand downstream gene expression modulation in SW480 cells comparedto control groups.Conclusion: These findings showed that STAT3-decoy ODNs is anefficient inducer of cell death and apoptosis in the Erlotinib resistantSW480 colon cancer cell line. Inhibition of STAT3 by cis-element doublestrandedoligodeoxynucleotide (ODNs) strategy holds great promise forthe effective treatment of colon cancer.

Keywords:

Colon cancer , Decoy oligodeoxynucleotide , STAT3 transcription factor , Erlotinib , Drug resistance