Zhang Wan-Fu, Jin Wen-Di, Li Bo, Wang Ming-Chun, Li Xiao-Gang, Mao Wen-Yuan, Luo Kai-Yuan
Department of General Surgery, The Second People's Hospital of Yunnan Province, Kunming, Yunnan 650500, P.R. China.
Oncol Rep. 2014 Aug;32(2):635-40. doi: 10.3892/or.2014.3255. Epub 2014 Jun 12.
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.
碘 - 125（¹²⁵I）粒子植入可作为不可切除进展期胃癌的重要辅助治疗手段。然而，近距离放射治疗的放射生物学机制尚不清楚。因此，我们在人胃癌异种移植模型中研究了持续低能量¹²⁵I照射对细胞周期分布、细胞凋亡、核因子κB（NF - κB）和血管内皮生长因子（VEGF）表达以及肿瘤生长的影响。为建立胃癌动物模型，将SGC - 7901细胞手术植入小鼠体内。60只携带SGC - 7901胃癌异种移植瘤的小鼠随机分为2组。对照组（n = 30）植入假粒子（0毫居里）；治疗组（n = 30）植入¹²⁵I粒子（0.6毫居里）。照射后28天，通过流式细胞术检测细胞凋亡。荧光显微镜检测肿瘤样本中VEGF和NF - κB的强烈免疫荧光，分别通过实时聚合酶链反应（PCR）和蛋白质免疫印迹分析评估NF - κB和VEGF mRNA及蛋白表达的变化。在¹²⁵I粒子植入后0 - 28天测量肿瘤体积和重量。¹²⁵I粒子照射诱导显著的细胞凋亡和G2/M期阻滞。治疗后观察到肿瘤血管中VEGF和NF - κB免疫荧光强度降低。植入治疗组中NF - κB和VEGF mRNA及蛋白表达水平明显低于对照组。因此，¹²⁵I粒子植入抑制了肿瘤生长并减小了肿瘤体积。本研究表明，¹²⁵I粒子照射显著诱导人胃癌异种移植瘤细胞凋亡和细胞周期阻滞。¹²⁵I诱导的NF - κB和VEGF表达变化被认为是有效近距离放射治疗的潜在机制。
