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

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

doi:10.3892/ijo.2017.4062

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

Authors:
- Si-Jie Li
- Chun-Shui Liu
- Hai-Jun Li
- Yan Li
- Lei Zhou
- Jin-Cheng Li
- Yi-Chang Chen
- Tian-Qi Su
- De-Hai Yu
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Affiliations: Department of Breast Surgery, the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Cancer Center, the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Institute of Translational Medicine, the First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Clinical Medicine, Norman Bethune Health Science Center, Jilin University, Changchun, Jilin 130021, P.R. China
Published online on: July 3, 2017 https://doi.org/10.3892/ijo.2017.4062
Pages: 949-958

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Abstract

Breast cancer is the most common carcinoma among Chinese women. Interferon α (IFNα) 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 IFNα, we constructed an engineered IFNα-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 IFNα 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.

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