A novel engineered interferon-alpha hybrid molecule increases anticancer efficacy of doxorubicin in breast cancer chemotherapy

作者：Li, Si-Jie; Liu, Chun-Shui; Li, Hai-Jun; Li, Yan; Zhou, Lei; Li, Jin-Cheng; Chen, Yi-Chang; Su, Tian-Qi; Yu, De-Hai^*

来源：International Journal of Oncology, 2017, 51(3): 949-958.

DOI：10.3892/ijo.2017.4062

• phage display library
• interferon a
• doxorubicin
• breast cancer

Breast cancer is the most common carcinoma among Chinese women. Interferon a (IFN alpha) has been used to treat various types of cancer, including breast cancer, but its antitumor activity is relative low, which significantly hinders its clinical application. In this study, we utilized a Ph.D.-12 peptide library screening system to identify a short peptide that specifically binds to MCF-7 breast cancer cells. By fusing the MCF-7 binding peptide (MBP) to the C-terminus of IFN alpha, we constructed an engineered IFN alpha-MBP fusion molecule (IMBP), and applied this novel fusion protein to the treatment of breast cancer. We found that IMBP exhibited significantly higher activity than wild-type IFN alpha in inhibiting cell growth and inducing cell apoptosis. Additionally, IMBP potentiated the therapeutic efficacy of doxorubicin-based breast cancer chemotherapy via the activation of cell cycle arrest and cell apoptosis pathway genes including p53, p21, CDK2, cyclin A, caspase 9, Bcl-2 and Bax. The enhanced activity of the synthetic IMBP was also associated with the activation of signal transducer and activation of transcription 1 (STAT1) pathway target genes (STAT1, IFIT1, IFITM1 and MX1). This study evaluated the potential value of the synthetic IMBP as a novel anti-breast cancer agent.

• 出版日期2017-9
• 单位吉林大学