title: Effect of brachytherapy on NF-κB and VEGF in gastric carcinoma xenografts.
abstract: Iodine-125 (125I) seed irradiation can be used as an important supplementary treatment for unresectable advanced gastric cancer. However, the radiobiological mechanism underlying brachytherapy remains unclear. Therefore, we investigated the influence of continuous and low-energy 125I irradiation on the cell cycle distribution, apoptosis, expression of NF-κB and VEGF and tumor growth in a human gastric cancer xenograft model. To create an animal model of gastric cancer, SGC-7901 cells were surgically implanted into mice. The 60 mice bearing SGC-7901 gastric cancer xenografts were randomly separated into 2 groups. Sham seeds (0 mCi) were implanted into the control group (n=30); 125I seeds (0.6 mCi) were implanted into the treatment group (n=30). At 28 days after irradiation, apoptosis was detected by flow cytometry. fluorescence micrograph detected intense VEGF and NF-κB immunofluorescence in the tumor samples, and changes in NF-κB and VEGF mRNA and protein expression were assessed by real-time PCR and western blot analysis, respectively. The tumor volume and weight were measured 0-28 days after 125I seed implantation. 125I seed irradiation induced significant apoptosis and G2/M phase arrest. Reduction in the intensities of VEGF and NF-κB immunofluorescence in tumor vessels was observed after treatment. NF-κB and VEGF mRNA and protein expression levels were substantially lower in the implantation treatment group than in the control group. Consequently, 125I seed implantation inhibited cancer growth and reduced cancer volume. The present study revealed that 125I seed irradiation significantly induced apoptosis and cell cycle arrest in the human gastric cancer xenografts. 125I-induced changes in NF-κB and VEGF expression are suggested as potential mechanisms underlying effective brachytherapy.
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Wan-Fu
authors.initials: WF
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Wen-Di
authors.initials: WD
authors.lastname: Jin
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Wang
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Li
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Mao
authors.affiliation: Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
authors.forename: Kai-Yuan
authors.initials: KY
authors.lastname: Luo
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001918:Brachytherapy / Q000379:methods*; D002453:Cell Cycle / Q000528:radiation effects; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D017346:Protein Serine-Threonine Kinases; D042461:Vascular Endothelial Growth Factor A; D000097782:NF-kappaB-Inducing Kinase; C467480:vascular endothelial growth factor A, mouse