Attenuated measles virus overcomes radio‑ and chemoresistance in human breast cancer cells by inhibiting the non‑homologous end joining pathway

减毒麻疹病毒通过抑制非同源末端连接途径克服人类乳腺癌细胞的放射和化学抗性

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作者:Ben Yang #, Jingwei Shi #, Zhi Sun, Dongdong Zhu, Xuesong Xu

Abstract

Breast cancer is the most commonly diagnosed cancer and is the second leading cause of death in women. However, resistance to radio‑ and chemotherapy remains one of the major difficulties in the treatment of breast cancer. Therefore, the aim of the present study was to identify novel regimens to overcome treatment resistance in patients with breast cancer. The results of the present study demonstrated that the attenuated Edmonston‑B vaccine strain of the measles virus (MV‑Edm) significantly re‑sensitized breast cancer cells to doxorubicin and ionizing radiation. Mechanistically, MV‑Edm reduced DNA double strand repair efficiency by decreasing the mRNA and protein expression levels of p53‑binding protein 1 and disassembling the non‑homologous end joining (NHEJ) complex. NHEJ deficiency, which was achieved using DNA ligase IV knockout via CRISPR/Cas9, resulted in failure to overcome resistance mediated by MV‑Edm infection. As a result of the significant synergy between attenuated MV and radio‑ or chemotherapy, MV‑Edm provides a novel strategy for the treatment of radio‑ and chemoresistant breast cancer.

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