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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), 2024. Published by Science Publishing Group

Keywords

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

References
[1] Chen W, Sun K, Zheng R, Zeng H, Zhang S, Xia C, Yang Z, Li H, Zou X, He J. Cancer incidence and mortality in China, 2014. Chin J Cancer Res. 2018; 30 (1): 1-12.
[2] Zappa C, Mousa SA. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res, 2016, 5 (3): 288-300.
[3] NCCN guidelines for lung adenocarcinoma version 1. 2022. n.d.
[4] Jiang W, Jin G, Cai F, Chen X, Cao N, Zhang X, Liu J, Chen F, Wang F, Dong W, Zhuang H, Hua ZC. Extracellular signal-regulated kinase 5 increases radioresistance of lung cancer cells by enhancing the DNA damage response. Exp Mol Med. 2019; 51 (2): 19.
[5] Schwartz S. Porphyrins and porphyrin precursors in human and experimental porphyria. Fed Proc. 1955; 14 (3): 717-22.
[6] Kostron H, Swartz MR, Miller DC, Martuza RL. The interaction of hematoporphyrin derivative, light, and ionizing radiation in a rat glioma model. Cancer. 1986; 57 (5): 964-70.
[7] Yin HT, Yu Y. Identifiction of the of hematoporphyrin derivative in lung adenocarcinoma using integrated network analysis [J]. Biological Research, 2019, 2 (52).
[8] Cao S, Jin S, Shen J, Cao J, Zhang H, Meng Q, Wang C, Zhang A, Zhang P, Yu Y. Selected patients can benefit more from the management of etoposide and platinum-based chemotherapy and thoracic irradiation-a retrospective analysis of 707 small cell lung cancer patients. Oncotarget. 2017; 8 (5): 8657-8669.
[9] Costley D, Mc Ewan C, Fowley C, McHale AP, Atchison J, Nomikou N, Callan JF. Treating cancer with sonodynamic therapy: a review. Int J Hyperthermia. 2015; 31 (2): 107-17.
[10] Brown SB, Brown EA, Walker I. The present and future role of photodynamic therapy in cancer treatment. Lancet Oncol. 2004; 5 (8): 497-508.
[11] Almeida RD, Manadas BJ, Carvalho AP, Duarte CB. Intracellular signaling mechanisms in photodynamic therapy. Biochim Biophys Acta. 2004; 1704 (2): 59-86.
[12] Schaffer M, Ertl-Wagner B, Schaffer PM, Kulka U, Jori G, Duhmke E, Hofstetter A. The Application of Photofrin II as a sensitizing agent for ionizing radiation--a new approach in tumor therapy? Curr Med Chem. 2005; 12 (10): 1209-15.
[13] Xia L, Guan W, Wang D, Zhang YS, Zeng LL, Li ZP, Wang G, Yang ZZ. Killing effect of Ad5/F35-APE1 siRNA recombinant adenovirus in combination with hematoporphrphyrin derivative-mediated photodynamic therapy on human nonsmall cell lung cancer. Biomed Res Int. 2013; 2013: 957913.
[14] Jego G, Hazoume A, Seigneuric R, Garrido C. Targeting heat shock proteins in cancer. Cancer Lett. 2013; 332 (2): 275-85.
[15] Beere HM. "The stress of dying": the role of heat shock proteins in the regulation of apoptosis. J Cell Sci. 2004; 117 (Pt 13): 2641-51.
[16] Chatterjee S, Bhattacharya S, Socinski MA, Burns TF. HSP90 inhibitors in lung cancer: promise still unfulfilled. Clin Adv Hematol Oncol. 2016; 14 (5): 346-56.
[17] Sun Y, Huang YH, Huang FY, Mei WL, Liu Q, Wang CC, Lin YY, Huang C, Li YN, Dai HF, Tan GH. 3'-epi-12beta-hydroxyfroside, a new cardenolide, induces cytoprotective autophagy via blocking the Hsp90/Akt/mTOR axis in lung cancer cells. Theranostics. 2018; 8 (7): 2044-2060.
[18] Coskunpinar E, Akkaya N, Yildiz P, Oltulu YM, Aynaci E, Isbir T, Yaylim I. The significance of HSP90AA1, HSP90AB1 and HSP90B1 gene polymorphisms in a Turkish population with non-small cell lung cancer. Anticancer Res. 2014; 34 (2): 753-7.
[19] Sequist LV, Gettinger S, Senzer NN, Martins RG, Janne PA, Lilenbaum R, Gray JE, Iafrate AJ, Katayama R, Hafeez N, Sweeney J, Walker JR, Fritz C, Ross RW, Grayzel D, Engelman JA, Borger DR, Paez G, Natale R. Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol. 2010; 28 (33): 4953-60.
[20] Cai J, Li R, Xu X, Zhang L, Lian R, Fang L, Huang Y, Feng X, Liu X, Li X, Zhu X, Zhang H, Wu J, Zeng M, Song E, He Y, Yin Y, Li J, Li M. CK1alpha suppresses lung tumour growth by stabilizing PTEN and inducing autophagy. Nat Cell Biol. 2018; 20 (4): 465-478.
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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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