Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells.
ONCOLOGY REPORTS(2020)
摘要
Iodine-125 (I-125) 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 I-125 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 I-125 seed radiation significantly inhibited cell proliferation, and induced DNA damage and G2/M cell cycle arrest in both ESCC cell lines. I-125 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. I-125 seed radiation induced autophagic flux in both ESCC cell lines, and autophagy inhibition by 3-methyladenine enhanced radiosensitivity. Furthermore I-125 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 I-125 seed radiation on endoplasmic reticulum stress, autophagy, apoptosis, paraptotic vacuoles and reduced cell viability. In vivo experiments showed that I-125 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, I-125 seed radiation induces cell death through both apoptosis and paraptosis; and at the same time initiates protective autophagy. Additionally, I-125 seed radiation-induced apoptosis, paraptosis and autophagy was considerably mediated by ROS.
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关键词
I-125 seed radiation,apoptosis,autophagy,paraptosis,esophageal cancer
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