title: 125I Seeds Radiation Induces Paraptosis-Like Cell Death via PI3K/AKT Signaling Pathway in HCT116 Cells.
abstract: 125I seeds brachytherapy implantation has been extensively performed in unresectable and rerecurrent rectal carcinoma. Many studies on the cancer-killing activity of125I seeds radiation mainly focused on its ability to trigger apoptosis, which is the most well-known and dominant type of cell death induced by radiation. However our results showed some unique morphological features such as cell swelling, cytoplasmic vacuolation, and plasma membrane integrity, which is obviously different to apoptosis. In this study, clonogenic proliferation was carried out to assay survival fraction. Transmission electron microscopy was used to analyze ultrastructural and evaluate morphologic feature of HCT116 cells after exposure to125I seeds radiation. Immunofluorescence analysis was used to detect the origin of cytoplasmic vacuoles. Flow cytometry analysis was employed to detect the size and granularity of HCT116 cells. Western blot was performed to measure the protein level of AIP1, caspase-3, AKT, p-Akt (Thr308), p-Akt (Ser473), and β-actin. We found that125I seeds radiation activated PI3K/AKT signaling pathway and could trigger paraptosis-like cell death. Moreover, inhibitor of PI3K/AKT signaling pathway could inhibit paraptosis-like cell death induced by125I seeds radiation. Our data suggest that125I seeds radiation can induce paraptosis-like cell death via PI3K/AKT signaling pathway.
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China; School of Medicine, Anhui University of Science and Technology, Huainan, Anhui 232001, China.
authors.forename: Lelin
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Radiation Oncology, Peking University 3rd Hospital, Haidian District, Beijing 100191, China.
authors.forename: Junjie
authors.identifier: 0000-0002-4092-2232
authors.initials: J
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects*; D001918:Brachytherapy / Q000009:adverse effects*; D045325:HCT116 Cells / Q000528:radiation effects / Q000648:ultrastructure; D006801:Humans; D007457:Iodine Radioisotopes / Q000009:adverse effects*; D046529:Microscopy, Electron, Transmission; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis; D011836:Radiation Tolerance; D012004:Rectal Neoplasms / Q000235:genetics / Q000473:pathology / Q000532:radiotherapy*; D015398:Signal Transduction / Q000528:radiation effects
chemical_list: D007457:Iodine Radioisotopes; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt