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Increasing the colon cancer cells sensitivity toward radiation therapy via application of Oct4–Sox2 complex decoy oligodeoxynucleotides

Abstract

Low sensitivity of cancer stem cells toward regular cancer therapy strategies is an important issue in the field of cancer remedy. The concept of cancer stem cell elimination has been a topic of interest in the field of molecular medicine for a long time. At the current study, it was aimed to elevate the sensitivity of cancer stem-like cells toward radiotherapy by treating with Oct4–Sox2 complex decoy oligodeoxynucleotides (ODNs). After treating HT29 and HT29-ShE cells with Oct4–Sox2 complex decoy ODNs, and analyzing the cellular uptake and localization of decoys, treated cells and control groups were subjected to irradiation by fractionated 6MV X-ray with a final dose of 2 Gy. Thereafter, the influence of radiotherapy on ODNs treated groups and control group was investigated on cell viability, cell cycle, apoptosis, colonosphere formation and scratch assay. Cellular uptake and localization assays demonstrated that decoy ODNs can efficiently be transfected to the cells and reside in subcellular compartment, where they pose their action on gene regulation. Post radiotherapy analysis indicated statistical significance in decoy ODNs treated cells by means of lower cell viability, cell cycle arrest in G2/M phase, increased cellular apoptosis, and reduced cell motility. Also, formed colonospheres were smaller in size and fewer in numbers. Considering the role of Oct4, and Sox2 transcription factors in signaling pathways of preserving stemness and inducing reverse EMT, application of decoy strategy could increase the sensitivity of cancer cells toward irradiation, which has a potential to eliminate the cancerous cells from tumors and support cancer treatment.

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Acknowledgements

This study was supported by Zanjan University of Medical Sciences (Grant Number A-12-1357-1, Ethical Code ZUMS.REC.1378.379).

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Conception and design the study: BJ. Collection, assembly of data and manuscript writing: BJ, HR, MM, ZS, ZT, YM. Final approval of manuscript: BJ and LN.

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Correspondence to Leila Nasehi.

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Leila Nasehi received the Grant from Zanjan University of Medical Sciences. All the authors declare no financial or commercial conflict of interests that could negatively influence the study.

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No human or animal was involved in this study.

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Johari, B., Rezaeejam, H., Moradi, M. et al. Increasing the colon cancer cells sensitivity toward radiation therapy via application of Oct4–Sox2 complex decoy oligodeoxynucleotides. Mol Biol Rep 47, 6793–6805 (2020). https://doi.org/10.1007/s11033-020-05737-4

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  • DOI: https://doi.org/10.1007/s11033-020-05737-4

Keywords

  • Radiotherapy
  • Decoy ODNs
  • Colon cancer
  • Cancer stem-like cell
  • Differentiation therapy