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Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells

Received: 29 September 2022     Accepted: 19 October 2022     Published: 28 October 2022
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Abstract

Background: Radiotherapy effectiveness is drastically reduced in malignant tumors with low radiosensitivity. Combining hematoporphyrin derivatives (HPDs) with radiotherapy may have radiosensitizing effects, but radiosensitization mechanisms of HPDs in lung adenocarcinoma remains unclear. This study used in vitro experiments to verify whether HPDs could increase the sensitivity of lung adenocarcinoma cells to radiotherapy, and to determine how HPDs induce radiosensitization. Methods: Cloning experiments were performed on lung adenocarcinoma (A549) cells under three conditions: untreated, X-ray radiation alone, and HPDs combined with X-ray radiation. We analyzed results from previous research screening target gene HSP90AA1, then used western blotting to detect autophagosome formation. Differences in AKT, mTOR, and LC3 expression before and after X-ray/HPD treatment in A549 cells were analyzed. Results: Optimal HPD concentration and X-ray dose were 10 and 10 Gy, respectively. The combination of HPDs and X-ray inhibited proliferation and promoted apoptosis of A549 cells in a dose-dependent manner. Western blotting revealed few autophagosomes in the control group, whereas autophagosomes increased significantly in A549 cells after X-ray irradiation. Combining HPDs and X-ray decreased autophagosome numbers. Compared to X-ray only, HPDs + X-ray resulted in decreased LC3II expression and LC3II/LC3I ratio. Additionally, the LC3II/LC3I ratio was higher in the X-ray group than in the control group. Conclusions: The combination of X-ray irradiation and HPDs inhibited cell proliferation and induced radiosensitization in A549 cells. The radiosensitizing effect of HSP90AA1 may be related to autophagy. Thus, HSP90AA1 is a potential biomarker for enhanced radiosensitivity after HPD treatment.

Published in Radiation Science and Technology (Volume 8, Issue 4)
DOI 10.11648/j.rst.20220804.11
Page(s) 51-57
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2022. Published by Science Publishing Group

Keywords

Lung Adenocarcinoma, X-ray, Radiosensitization, Hematoporphyrin Derivatives, Autophagy

References
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  • APA Style

    Hongtao Yin, Hongxu Zhang, Chunbo Wang, Wencheng Shao. (2022). Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells. Radiation Science and Technology, 8(4), 51-57. https://doi.org/10.11648/j.rst.20220804.11

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    ACS Style

    Hongtao Yin; Hongxu Zhang; Chunbo Wang; Wencheng Shao. Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells. Radiat. Sci. Technol. 2022, 8(4), 51-57. doi: 10.11648/j.rst.20220804.11

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    AMA Style

    Hongtao Yin, Hongxu Zhang, Chunbo Wang, Wencheng Shao. Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells. Radiat Sci Technol. 2022;8(4):51-57. doi: 10.11648/j.rst.20220804.11

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  • @article{10.11648/j.rst.20220804.11,
      author = {Hongtao Yin and Hongxu Zhang and Chunbo Wang and Wencheng Shao},
      title = {Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells},
      journal = {Radiation Science and Technology},
      volume = {8},
      number = {4},
      pages = {51-57},
      doi = {10.11648/j.rst.20220804.11},
      url = {https://doi.org/10.11648/j.rst.20220804.11},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.rst.20220804.11},
      abstract = {Background: Radiotherapy effectiveness is drastically reduced in malignant tumors with low radiosensitivity. Combining hematoporphyrin derivatives (HPDs) with radiotherapy may have radiosensitizing effects, but radiosensitization mechanisms of HPDs in lung adenocarcinoma remains unclear. This study used in vitro experiments to verify whether HPDs could increase the sensitivity of lung adenocarcinoma cells to radiotherapy, and to determine how HPDs induce radiosensitization. Methods: Cloning experiments were performed on lung adenocarcinoma (A549) cells under three conditions: untreated, X-ray radiation alone, and HPDs combined with X-ray radiation. We analyzed results from previous research screening target gene HSP90AA1, then used western blotting to detect autophagosome formation. Differences in AKT, mTOR, and LC3 expression before and after X-ray/HPD treatment in A549 cells were analyzed. Results: Optimal HPD concentration and X-ray dose were 10 and 10 Gy, respectively. The combination of HPDs and X-ray inhibited proliferation and promoted apoptosis of A549 cells in a dose-dependent manner. Western blotting revealed few autophagosomes in the control group, whereas autophagosomes increased significantly in A549 cells after X-ray irradiation. Combining HPDs and X-ray decreased autophagosome numbers. Compared to X-ray only, HPDs + X-ray resulted in decreased LC3II expression and LC3II/LC3I ratio. Additionally, the LC3II/LC3I ratio was higher in the X-ray group than in the control group. Conclusions: The combination of X-ray irradiation and HPDs inhibited cell proliferation and induced radiosensitization in A549 cells. The radiosensitizing effect of HSP90AA1 may be related to autophagy. Thus, HSP90AA1 is a potential biomarker for enhanced radiosensitivity after HPD treatment.},
     year = {2022}
    }
    

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  • TY  - JOUR
    T1  - Investigating Radiosensitization Mechanisms of Hematoporphyrin Derivatives in Lung Adenocarcinoma Cells
    AU  - Hongtao Yin
    AU  - Hongxu Zhang
    AU  - Chunbo Wang
    AU  - Wencheng Shao
    Y1  - 2022/10/28
    PY  - 2022
    N1  - https://doi.org/10.11648/j.rst.20220804.11
    DO  - 10.11648/j.rst.20220804.11
    T2  - Radiation Science and Technology
    JF  - Radiation Science and Technology
    JO  - Radiation Science and Technology
    SP  - 51
    EP  - 57
    PB  - Science Publishing Group
    SN  - 2575-5943
    UR  - https://doi.org/10.11648/j.rst.20220804.11
    AB  - Background: Radiotherapy effectiveness is drastically reduced in malignant tumors with low radiosensitivity. Combining hematoporphyrin derivatives (HPDs) with radiotherapy may have radiosensitizing effects, but radiosensitization mechanisms of HPDs in lung adenocarcinoma remains unclear. This study used in vitro experiments to verify whether HPDs could increase the sensitivity of lung adenocarcinoma cells to radiotherapy, and to determine how HPDs induce radiosensitization. Methods: Cloning experiments were performed on lung adenocarcinoma (A549) cells under three conditions: untreated, X-ray radiation alone, and HPDs combined with X-ray radiation. We analyzed results from previous research screening target gene HSP90AA1, then used western blotting to detect autophagosome formation. Differences in AKT, mTOR, and LC3 expression before and after X-ray/HPD treatment in A549 cells were analyzed. Results: Optimal HPD concentration and X-ray dose were 10 and 10 Gy, respectively. The combination of HPDs and X-ray inhibited proliferation and promoted apoptosis of A549 cells in a dose-dependent manner. Western blotting revealed few autophagosomes in the control group, whereas autophagosomes increased significantly in A549 cells after X-ray irradiation. Combining HPDs and X-ray decreased autophagosome numbers. Compared to X-ray only, HPDs + X-ray resulted in decreased LC3II expression and LC3II/LC3I ratio. Additionally, the LC3II/LC3I ratio was higher in the X-ray group than in the control group. Conclusions: The combination of X-ray irradiation and HPDs inhibited cell proliferation and induced radiosensitization in A549 cells. The radiosensitizing effect of HSP90AA1 may be related to autophagy. Thus, HSP90AA1 is a potential biomarker for enhanced radiosensitivity after HPD treatment.
    VL  - 8
    IS  - 4
    ER  - 

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Author Information
  • Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China

  • Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, China

  • Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China

  • Department of Radiation Physics, Harbin Medical University Cancer Hospital, Harbin, China

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