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International Journal of Oncology
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Print ISSN: 1019-6439 Online ISSN: 1791-2423
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August-2014 Volume 45 Issue 2

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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.

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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.

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

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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.

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International Journal of Functional Nutrition

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

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International Journal of Epigenetics

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

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Article

Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer

  • Authors:
    • Soichiro Honjo
    • Jaffer A. Ajani
    • Ailing W. Scott
    • Qiongrong Chen
    • Heath D. Skinner
    • John Stroehlein
    • Randy L. Johnson
    • Shumei Song
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, Department of Gastroenterology, Hepatology and Nutrition, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA, Department of Biochemistry and Molecular Biology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA
  • Pages: 567-574
    |
    Published online on: May 21, 2014
       https://doi.org/10.3892/ijo.2014.2450
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Abstract

Our clinical study indicates esophageal adenocarcinoma patients on metformin had a better treatment response than those without metformin. However, the effects of metformin and the mechanisms of its action in esophageal cancer (EC) are unclear. EC cell lines were used to assess the effects of metformin alone or in combination with 5-fluorouracil on survival and apoptosis. RPPA proteomic array and immunoblots were used to identify signaling affected by metformin. Standard descriptive statistical methods were used. Reduction in cell survival and induction of apoptosis by metformin were observed in several EC cell lines. The use of metformin in combination with 5-FU significantly sensitized EC cells to the cytotoxic effect of 5-FU. RPPA array demonstrated that metformin decreased various oncogenes including PI3K/mTORsignaling and survival/cancer stem cell-related genes in cells treated with metformin compared with its control. Immunoblots and transcriptional analyses further confirm that metformin downregulated these CSC-related genes and the components of the mTOR pathway in a dose‑dependent manner. Sorted ALDH-1+ cell tumor sphere forming capacity was preferentially reduced by metformin. Finally, metformin reduced tumor growth in vivo and when combined with FU, there was synergistic reduction in tumor growth. Metformin inhibits EC cell growth and sensitizes EC cells to 5-FU cytotoxic effects by targeting CSCs and the components of mTOR. The present study supports our previous clinical observations that the use of metformin is beneficial to EC patients. Metformin can complement other therapeutic combinations to effectively treat EC patients.
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Copy and paste a formatted citation
Spandidos Publications style
Honjo S, Ajani JA, Scott AW, Chen Q, Skinner HD, Stroehlein J, Johnson RL and Song S: Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. Int J Oncol 45: 567-574, 2014.
APA
Honjo, S., Ajani, J.A., Scott, A.W., Chen, Q., Skinner, H.D., Stroehlein, J. ... Song, S. (2014). Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. International Journal of Oncology, 45, 567-574. https://doi.org/10.3892/ijo.2014.2450
MLA
Honjo, S., Ajani, J. A., Scott, A. W., Chen, Q., Skinner, H. D., Stroehlein, J., Johnson, R. L., Song, S."Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer". International Journal of Oncology 45.2 (2014): 567-574.
Chicago
Honjo, S., Ajani, J. A., Scott, A. W., Chen, Q., Skinner, H. D., Stroehlein, J., Johnson, R. L., Song, S."Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer". International Journal of Oncology 45, no. 2 (2014): 567-574. https://doi.org/10.3892/ijo.2014.2450
Copy and paste a formatted citation
x
Spandidos Publications style
Honjo S, Ajani JA, Scott AW, Chen Q, Skinner HD, Stroehlein J, Johnson RL and Song S: Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. Int J Oncol 45: 567-574, 2014.
APA
Honjo, S., Ajani, J.A., Scott, A.W., Chen, Q., Skinner, H.D., Stroehlein, J. ... Song, S. (2014). Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer. International Journal of Oncology, 45, 567-574. https://doi.org/10.3892/ijo.2014.2450
MLA
Honjo, S., Ajani, J. A., Scott, A. W., Chen, Q., Skinner, H. D., Stroehlein, J., Johnson, R. L., Song, S."Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer". International Journal of Oncology 45.2 (2014): 567-574.
Chicago
Honjo, S., Ajani, J. A., Scott, A. W., Chen, Q., Skinner, H. D., Stroehlein, J., Johnson, R. L., Song, S."Metformin sensitizes chemotherapy by targeting cancer stem cells and the mTOR pathway in esophageal cancer". International Journal of Oncology 45, no. 2 (2014): 567-574. https://doi.org/10.3892/ijo.2014.2450
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