title: Continuous low-dose irradiation by I-125 seeds induces apoptosis of gastric cancer cells regardless of histological origin.
abstract: The efficacy of conventional radiation therapy for gastric cancer is controversial. In this study, we evaluated the in vitro and in vivo effects of continuous low-dose-rate irradiation by I-125 seeds on different histological types of gastric cancer cell lines. Three human gastric cancer cell lines (MKN74, MKN45, and NUGC4) were treated with or without continuous low-dose irradiation by I-125 seeds in vitro and in vivo. Cell viability, apoptosis, caspase-3 assay, and cell-cycle distribution were examined in vitro. Body weight and tumor volumes of BALB/c nude mice bearing MKN74, MKN45, and NUGC4 gastric cancer xenografts were measured, and in vivo cell proliferation and apoptosis assays were performed by Ki67 and TUNEL staining, respectively. Continuous low-dose-rate irradiation by I-125 seeds reduced cell viability and induced cell apoptosis through the activation of caspase-3, and led to the accumulation of cells in the G 2/M phase in vitro. It also suppressed the growth of gastric cancer xenografts in nude mice, while inhibiting cell proliferation and inducing apoptosis as demonstrated by Ki67 and TUNEL staining. Therefore, our data suggest that continuous low-dose-rate irradiation by I-125 seeds could be a promising new option for gastric cancer treatment, regardless of histological origin.
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takabayashi
authors.affiliation: Center for Diagnostic and Therapeutic Endoscopy; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kashiwagi
authors.affiliation: Department of Radiology; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kawata
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sato
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Katsuyoshi
authors.initials: K
authors.lastname: Matsuoka
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Hisamatsu
authors.affiliation: Cancer Center; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Takaishi
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Hibi
authors.affiliation: Center for Diagnostic and Therapeutic Endoscopy; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Ogata
authors.affiliation: Division of Research and Development for Minimally Invasive Treatment; Cancer Center; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Naohisa
authors.initials: N
authors.lastname: Yahagi
authors.affiliation: Department of Surgery; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Kitagawa
authors.affiliation: Department of Radiology; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Shigematsu
authors.affiliation: Division of Gastroenterology and Hepatology; Department of Internal Medicine; School of Medicine; Keio University; Tokyo, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Kanai
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D018279:Carcinoma, Signet Ring Cell / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects; D064593:Heterografts; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D007457:Iodine Radioisotopes
keywords: I-125 seed irradiation; apoptosis; caspase; cell cycle; gastric cancer