Application of decoy oligodeoxynucleotides strategy for inhibition of cell growth and reduction of metastatic properties in nonresistant and erlotinib‐resistant SW480 cell line
| Autor: | Behrooz Johari, Mojtaba Fathi, Zoleykha Asadi, Elham Rismani, Zahra Bigdelou |
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| Rok vydání: | 2021 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cell cycle checkpoint Cell Survival Apoptosis 03 medical and health sciences 0302 clinical medicine Cell Movement Cell Line Tumor medicine Humans Neoplasm Metastasis STAT3 Cell Proliferation Cell Death biology Cell growth Chemistry Cell Cycle Cell Cycle Checkpoints Cell Biology General Medicine Transfection Cell cycle 030104 developmental biology Oligodeoxyribonucleotides Drug Resistance Neoplasm 030220 oncology & carcinogenesis Colonic Neoplasms biology.protein Cancer research Erlotinib Decoy medicine.drug |
| Zdroj: | Cell Biology International. 45:1001-1014 |
| ISSN: | 1095-8355 1065-6995 |
| Popis: | Signal transducer and activator of transcription 3 (STAT3) is a critical regulator for angiogenesis, cell cycle progression, apoptosis, and drug resistance. Resistance toward EGF receptor (EGFR) inhibitors is a significant clinical concern for metastatic colon cancer patients. The present study aimed to evaluate the blocking influences of STAT3 decoy oligodeoxynucleotides (ODNs) on the STAT3 survival signaling pathway in Erlotinib-resistant and non-resistant SW480 colon cancer cells. First, STAT3 decoy and scramble ODNs were designed according to STAT3 elements in the promoter region of the MYCT1 gene and tested for the interaction of STAT3 protein with designed ODNs via in silico molecular docking study. Then, the efficiency of transfection and subcellular localization of ODNs were assessed using flow cytometry and fluorescence microscopy, respectively. Cell viability, cell cycle and apoptosis tests, scratch and colony formation assays, and real-time PCR were also used to study the cancerous properties of cells. A considerable decrease in proliferation of colon cancer cells was observed with blockade of STAT3 signaling due to cell cycle arrest and induced apoptosis via down-regulation of cyclin D1 and Bcl-XL, respectively. Furthermore, upon transfecting STAT3 decoy ODNs, colony formation potential and migration activity in both SW480 colon cancer cell lines were decreased compared to control groups. From this study, it could be concluded that STAT3 is critical for cell growth inhibition and metastatic properties reduction of resistant SW480 colon cancer cells, therefore STAT3 decoy ODNs could be considered as potential therapeutics along with current remedies for treating drug-resistant colon cancer. This article is protected by copyright. All rights reserved. |
| Databáze: | OpenAIRE |
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