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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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September-2015 Volume 47 Issue 3

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Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

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Medicine International

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Article

Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage

  • Authors:
    • Elina Jokinen
    • Jussi P. Koivunen
  • View Affiliations / Copyright

    Affiliations: Department of Medical Oncology and Radiotherapy and Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, PB22 90029 OYS, Finland
  • Pages: 1103-1110
    |
    Published online on: July 2, 2015
       https://doi.org/10.3892/ijo.2015.3071
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Abstract

The dual targeting of PI3K-AKT-mTOR and Ras-Raf-MEK-ERK pathways is a potential anticancer therapy, but unfortunately, the response rate has been low in early phase clinical trials. Pre-clinical models have suggested that an apoptotic response to dual PI3K and MEK targeting is relatively rare and understanding apoptotic avoidance could lead to increased clinical efficiency. This study investigated solid cancer cell lines, which are known to be sensitive to dual PI3K and MEK inhibition but to have a limited apoptotic response. The cells were exposed to dual PI3K and MEK blockage in combination with a panel of additional pharmacological agents and cytotoxicity and apoptosis were analyzed. Our results indicated that the BH3 mimetic ABT-263, the HDAC inhibitor entinostat and the multikinase inhibitor dasatinib increased the cytotoxicity and apoptotic response of dual PI3K and MEK targeting. Furthermore, ABT-263 and entinostat was able to induce apoptosis in combination with single agent PI3K and MEK inhibitors. Protein expression, immunoprecipitation and siRNA knockdown models suggested that Bcl-xl and Mcl-1 were the most important factors circumventing PI3K and/or MEK inhibition-mediated apoptosis. The results suggest that the cytotoxicity of PI3K and/or MEK inhibitor treatments can be augmented by combinatory approaches targeting anti-apoptotic mediators Bcl-xl and Mcl-1.
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Copy and paste a formatted citation
Spandidos Publications style
Jokinen E and Koivunen JP: Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. Int J Oncol 47: 1103-1110, 2015.
APA
Jokinen, E., & Koivunen, J.P. (2015). Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. International Journal of Oncology, 47, 1103-1110. https://doi.org/10.3892/ijo.2015.3071
MLA
Jokinen, E., Koivunen, J. P."Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage". International Journal of Oncology 47.3 (2015): 1103-1110.
Chicago
Jokinen, E., Koivunen, J. P."Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage". International Journal of Oncology 47, no. 3 (2015): 1103-1110. https://doi.org/10.3892/ijo.2015.3071
Copy and paste a formatted citation
x
Spandidos Publications style
Jokinen E and Koivunen JP: Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. Int J Oncol 47: 1103-1110, 2015.
APA
Jokinen, E., & Koivunen, J.P. (2015). Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage. International Journal of Oncology, 47, 1103-1110. https://doi.org/10.3892/ijo.2015.3071
MLA
Jokinen, E., Koivunen, J. P."Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage". International Journal of Oncology 47.3 (2015): 1103-1110.
Chicago
Jokinen, E., Koivunen, J. P."Bcl-xl and Mcl-1 are the major determinants of the apoptotic response to dual PI3K and MEK blockage". International Journal of Oncology 47, no. 3 (2015): 1103-1110. https://doi.org/10.3892/ijo.2015.3071
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