Evaluation of STAT3 decoy oligodeoxynucleotides' synergistic effects on radiation and/or chemotherapy in metastatic breast cancer cell line

Resistance to radiotherapy and chemotherapy has been a major problem of conventional cancer therapies, which consequently leads to cancer relapse and cancer‐related death. It is known that cancer stem cells (CSCs) play a key role in therapy resistance and CSC‐based targeted therapies have been consi...

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Bibliographic Details
Published in:Cell biology international 2020-12, Vol.44 (12), p.2499-2511
Main Authors: Johari, Behrooz, Rahmati, Mohammad, Nasehi, Leila, Mortazavi, Yousef, Faghfoori, Mohammad Hasan, Rezaeejam, Hamed
Format: Article
Language:English
Subjects:
Apoptosis
Breast cancer
Cancer therapies
Cell cycle
Cell migration
Cell viability
Chemotherapy
decoy ODNs
G1 phase
Metastases
Methotrexate
Oligonucleotides
Radiation therapy
radiotherapy
Stat3 protein
STAT3 transcription factor
Statistical analysis
Stem cells
Transcription factors
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Summary:Resistance to radiotherapy and chemotherapy has been a major problem of conventional cancer therapies, which consequently leads to cancer relapse and cancer‐related death. It is known that cancer stem cells (CSCs) play a key role in therapy resistance and CSC‐based targeted therapies have been considered as a powerful tool for cancer treatment. In the current study, we investigated the synergistic effects of suppressing signal transducer and activator of transcription (STAT3) function by decoy ODNs on X‐irradiation (XI) and methotrexate (MTX) exposure as a combinational therapy in triple‐negative breast cancer (TNBC) MDA‐MB‐231 cells. Lipofectamine 2000® was used as a transfecting agent and the cells treated with Scramble ODNs (SCR) and decoy ODNs were subjected to irradiation with 2 Gy at single/fractionated (XI group) doses, different concentration of MTX group, and X‐irradiation‐methotrexate (XI/MTX group). Synergistic effects of STAT3 SCR and decoy ODNs on cells were investigated by cell viability (MTT), cell cycle profile, apoptosis rate, migration, and invasion assays. Statistical analysis of obtained data showed that STAT3 decoy ODNs significantly decreased the cell viability, arrested the growth at G0/G1 phase, increased apoptosis rate, and reduced migrated and invaded cells through transwell membrane, in XI, MTX, and XI/MTX exposed groups. Since STAT3 is a master transcription factor in breast cancer cells stemness, aggressiveness, TNBC's heterogeneity, and therapy resistance; therefore, inhibition of this transcription factor by decoy ODNs could increase antitumor efficiencies of XI and MTX exposure strategies. Accordingly, this method could have the potential to increase the efficiency of combination therapies.
ISSN:1065-6995
1095-8355
DOI:10.1002/cbin.11456