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Inhibition of Survivin Restores the Sensitivity of Breast Cancer Cells to Docetaxel and Vinblastine

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Abstract

Combination therapy is considered a viable strategy to overcome the resistance to chemotherapeutics. Survivin as a member of the inhibitor of apoptosis protein (IAP) family, which is involved in resistance to various drugs. We investigated the role of combination therapy in downregulating survivin and increasing drug’s efficacy in MDA-MB-231 cells. MTT assay and DAPI staining were applied to study the anti-proliferative activity and apoptosis response of the agents. Real-time RT-PCR and Western blot analysis were applied to study survivin mRNA and protein. Our findings showed that combined treatment of cells with docetaxel and vinblastine reduces survivin expression and consequently decreases the IC50 value of docetaxel from 70 to 5 nM (p < 0.05). Furthermore, combination therapy with deguelin, a survivin inhibitor, exerted a considerable enhancement in synergistic efficacy of docetaxel and vinblastine (p < 0.05). Survivin downregulation may thus be considered a potential strategy in increasing the efficacy of chemotherapeutics in cancer patients.

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Acknowledgments

The authors would like to acknowledge Dr. Tohidkia and Dr. Abdolalizadeh for their kind assistance in Western blot analysis and Mr. Sajjad Khani for contribution in Real-time PCR experiments. We are also grateful for the opportunity to work in Research Center for Pharmaceutical Nanotechnology in Tabriz University of medical sciences.

Conflict of interest

Authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Parisa Ghanbari, Mahsa Mohseni, Maryam Tabasinezhad & Nasser Samadi

  2. Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

    Parisa Ghanbari, Mahsa Mohseni, Maryam Tabasinezhad, Amir Ata Saei, Simin Sharifi, Mohammad Reza Rashidi & Nasser Samadi

  3. Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

    Bahman Yousefi & Nasser Samadi

  4. Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran

    Nasser Samadi

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  1. Parisa Ghanbari
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  2. Mahsa Mohseni
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Correspondence to Nasser Samadi.

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Parisa Ghanbari and Mahsa Mohseni contributed equally to this.

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Ghanbari, P., Mohseni, M., Tabasinezhad, M. et al. Inhibition of Survivin Restores the Sensitivity of Breast Cancer Cells to Docetaxel and Vinblastine. Appl Biochem Biotechnol 174, 667–681 (2014). https://doi.org/10.1007/s12010-014-1125-6

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