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Combination of S-1 and gefitinib increases the sensitivity to radiotherapy in lung cancer cells

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Abstract

Objective

To investigate the potential radiosensitization of S-1 and gefitinib in human non-small cell lung cancer (NSCLC) in vitro and in vivo.

Methods

The impact of radiation, 5-fluorouracil (5-Fu), and gefitinib on the proliferation and apoptosis of human NSCLC A549, H1299, H1975, and HCC827 cells was examined by MTT and flow cytometry. The effect of radiation, 5-Fu, and gefitinib on the clonogenicity of H1975 and HCC827 cells was determined by colony formation assay. The effect of radiation, 5-fluorouracil (5-Fu), and gefitinib on the EGFR, AKT, and ERK1/2 activation in H1975 cells was determined by Western blot. The therapeutic efficacy of radiation, S-1, and gefitinib in the growth of implanted H1975 tumors and the AKT activation in the tumors were examined in vivo and immunohistochemistry, respectively.

Results

Combination of radiation, 5-Fu, and gefitinib significantly inhibited the proliferation of H1975 cells and triggered their apoptosis, but not other NSCLC cells tested. The combination therapy significantly mitigated the clonogenicity and attenuated the activation of EGFR and AKT signaling in H1975 cells. Furthermore, combination of S-1, gefitinib, and radiation significantly inhibited the growth of implanted H1975 tumors in mice and remarkably reduced the AKT phosphorylation in the tumors.

Conclusions

Our data indicated that combination of S-1 and gefitinib significantly increased radiosensitivity of H1975 cells. The triple combination therapies may benefit patients with the EGFR T790M mutant NSCLC.

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Acknowledgements

We would like to thank Medjaden Bioscience Limited for their help in preparing the manuscript.

Funding

There was no special fund to support the study.

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Authors and Affiliations

  1. Department of Oncology, the First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China

    Jie Cui, Ya-Min Zhang, Ming-Zhi Ren & Shi-Xiong Wang

  2. Department of Radiotherapy, the Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China

    Min-Cong Wang

  3. Department of Oncology, the First Affiliated Hospital, Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Ke-Jun Nan

  4. Department of Radiotherapy, the First Affiliated Hospital of Xi’an Jiaotong University, No. 277 Yanta West Road, Xi’an, 710061, Shaanxi, People’s Republic of China

    Li-Ping Song

  5. The General Practice College of Xi’an Medical University, Xi’an, Shaanxi, People’s Republic of China

    Jie Cui, Ya-Min Zhang, Ming-Zhi Ren & Shi-Xiong Wang

Authors
  1. Jie Cui
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Correspondence to Ke-Jun Nan or Li-Ping Song.

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The authors declare no conflicts of interest.

Ethical approval

The animals experimental protocol was approved by the Animal Research and Care Committee of Xi’an Jiaotong University. This study does not have human participants performed by any of the authors.

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Cui, J., Wang, MC., Zhang, YM. et al. Combination of S-1 and gefitinib increases the sensitivity to radiotherapy in lung cancer cells. Cancer Chemother Pharmacol 81, 717–726 (2018). https://doi.org/10.1007/s00280-018-3539-2

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  • DOI: https://doi.org/10.1007/s00280-018-3539-2

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