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

• 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
• ISSN: 1065-6995; 1095-8355
• DOI: 10.1002/cbin.11456

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.