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Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells

  • Authors:
    • Chao Wang
    • Tian‑Kuan Li
    • Chu‑Hui Zeng
    • Rui Fan
    • Yong Wang
    • Guang‑Yu Zhu
    • Jin‑He Guo
  • View Affiliations / Copyright

    Affiliations: Jiangsu Key Laboratory of Molecular and Functional Imaging, Medical School, Southeast University, Nanjing, Jiangsu 210009, P.R. China, Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu 210009, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 2028-2044
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    Published online on: April 3, 2020
       https://doi.org/10.3892/or.2020.7576
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Abstract

Iodine‑125 (125I) seed brachytherapy has been proven to be a safe and effective treatment for advanced esophageal cancer; however, the mechanisms underlying its actions are not completely understood. In the present study, the anti‑cancer mechanisms of 125I seed radiation in human esophageal squamous cell carcinoma (ESCC) cells (Eca‑109 and KYSE‑150) were determined, with a particular focus on the mode of cell death. The results showed that 125I seed radiation significantly inhibited cell proliferation, and induced DNA damage and G2/M cell cycle arrest in both ESCC cell lines. 125I seed radiation induced cell death through both apoptosis and paraptosis. Eca‑109 cells were primarily killed by inducing caspase‑dependent apoptosis, with 6 Gy radiation resulting in the largest response. KYSE‑150 cells were primarily killed by inducing paraptosis, which is characterized by extensive cytoplasmic vacuolation. 125I seed radiation induced autophagic flux in both ESCC cell lines, and autophagy inhibition by 3‑methyladenine enhanced radiosensitivity. Furthermore 125I seed radiation induced increased production of reactive oxygen species (ROS) in both ESCC cell lines. Treatment with an ROS scavenger significantly attenuated the effects of 125I seed radiation on endoplasmic reticulum stress, autophagy, apoptosis, paraptotic vacuoles and reduced cell viability. In vivo experiments showed that 125I seed brachytherapy induced ROS generation, initiated cell apoptosis and potential paraptosis, and inhibited cell proliferation and tumor growth. In summary, the results demonstrate that in ESCC cells, 125I seed radiation induces cell death through both apoptosis and paraptosis; and at the same time initiates protective autophagy. Additionally, 125I seed radiation‑induced apoptosis, paraptosis and autophagy was considerably mediated by ROS.
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Copy and paste a formatted citation
Spandidos Publications style
Wang C, Li TK, Zeng CH, Fan R, Wang Y, Zhu GY and Guo JH: Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells. Oncol Rep 43: 2028-2044, 2020.
APA
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., & Guo, J. (2020). Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells. Oncology Reports, 43, 2028-2044. https://doi.org/10.3892/or.2020.7576
MLA
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., Guo, J."Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells". Oncology Reports 43.6 (2020): 2028-2044.
Chicago
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., Guo, J."Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells". Oncology Reports 43, no. 6 (2020): 2028-2044. https://doi.org/10.3892/or.2020.7576
Copy and paste a formatted citation
x
Spandidos Publications style
Wang C, Li TK, Zeng CH, Fan R, Wang Y, Zhu GY and Guo JH: Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells. Oncol Rep 43: 2028-2044, 2020.
APA
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., & Guo, J. (2020). Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells. Oncology Reports, 43, 2028-2044. https://doi.org/10.3892/or.2020.7576
MLA
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., Guo, J."Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells". Oncology Reports 43.6 (2020): 2028-2044.
Chicago
Wang, C., Li, T., Zeng, C., Fan, R., Wang, Y., Zhu, G., Guo, J."Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells". Oncology Reports 43, no. 6 (2020): 2028-2044. https://doi.org/10.3892/or.2020.7576
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