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Research ArticleExperimental Studies

The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells

SEO YUN KIM, EUN-HUI JEONG, TAE-GUL LEE, HYE-RYOUN KIM and CHEOL HYEON KIM
Anticancer Research June 2021, 41 (6) 2885-2894; DOI: https://doi.org/10.21873/anticanres.15070
SEO YUN KIM
1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea;
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EUN-HUI JEONG
1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea;
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TAE-GUL LEE
1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea;
2Department of Biotechnology, School of Life Sciences and Biotechnology, Korea University, Seoul, Republic of Korea
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HYE-RYOUN KIM
1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea;
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CHEOL HYEON KIM
1Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Republic of Korea;
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  • For correspondence: cheol@kcch.re.kr
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Abstract

Background/Aim: We evaluated the radiosensitizing effect of the combination treatment of trametinib, a MEK inhibitor, and temsirolimus, an mTOR inhibitor, on non-small-cell lung carcinoma (NSCLC) cells. Materials and Methods: The effects of combining trametinib and temsirolimus with radiation in NSCLC cell lines were evaluated using clonogenic survival and apoptosis assays. DNA double-strand breaks and cell cycle distribution were analyzed using flow cytometry. Tumor volume was measured to determine the radiosensitivity in lung cancer xenograft models. Results: Exposure of lung cancer cells to a combination of trametinib and temsirolimus reduced clonogenic survival and promoted radiation-induced apoptosis. Combined inhibition of MEK and mTOR induced prolonged expression of γH2AX after irradiation and resulted in prolonged G2/M cell cycle arrest after irradiation in A549 cells. In vivo studies revealed that co-administration of the drugs sensitizes lung cancer xenografts to radiotherapy. Conclusion: The combination of trametinib and temsirolimus can enhance lung cancer radiosensitivity in vitro and in vivo.

Key Words:
  • Lung cancer
  • MEK inhibitor
  • mTOR inhibitor
  • radiation
  • trametinib
  • temsirolimus
  • Received March 23, 2021.
  • Revision received May 11, 2021.
  • Accepted May 12, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (6)
Anticancer Research
Vol. 41, Issue 6
June 2021
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The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells
SEO YUN KIM, EUN-HUI JEONG, TAE-GUL LEE, HYE-RYOUN KIM, CHEOL HYEON KIM
Anticancer Research Jun 2021, 41 (6) 2885-2894; DOI: 10.21873/anticanres.15070

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The Combination of Trametinib, a MEK Inhibitor, and Temsirolimus, an mTOR Inhibitor, Radiosensitizes Lung Cancer Cells
SEO YUN KIM, EUN-HUI JEONG, TAE-GUL LEE, HYE-RYOUN KIM, CHEOL HYEON KIM
Anticancer Research Jun 2021, 41 (6) 2885-2894; DOI: 10.21873/anticanres.15070
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Keywords

  • lung cancer
  • MEK inhibitor
  • mTOR inhibitor
  • radiation
  • trametinib
  • temsirolimus
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