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.

Iodine‑125 seed radiation induces ROS‑mediated apoptosis, autophagy and paraptosis in human esophageal squamous cell carcinoma cells

“…Previous studies have attributed the anti-cancer effects of 125 I seed radiation to DNA damage, G2/M cell cycle arrest and apoptosis (8,14,37,38). DNA damage can be induced directly by radiation or indirectly by radiation-induced ROS (22).…”

125I seeds irradiation inhibits tumor growth and induces apoptosis by Ki-67, P21, survivin, livin and caspase-9 expression in lung carcinoma xenografts

“…125I seed implantation effectively inhibited tumor growth and reduced tumor volume, thus reducing tumor volume and improving the quality of animal survival. 125I irradiation inhibited the proliferation and induced cell apoptosis is the key mechanisms underlying the therapeutic effect of 125I seed implantation [39,40]. In the tumor microenvironment, 125I irradiation can inhibit cell proliferation by reducing the levels of Ki-67, as well as inducing apoptosis by increasing the level of P21 and reducing the levels of survivin and livin.…”

“…The anti-tumor effect of 125I seed has been studied in recent years, as well as the mechanism of 125I seed for induction of apoptosis and cell cycle inhibition [ 19 , 20 , 27 – 29 , 33 , 36 ], DNA hypomethylation [ 19 , 30 ] and anti-angiogenesis [ 27 , 37 , 38 ]. The most extensively studied mechanism is apoptosis [ 39 , 40 ]. More recently, studies have shown that apoptosis and inhibiting proliferation may play an essential role in the treatment effects of 125 I, but their mechanism of action has not been determined completely.…”

Combination of 125I brachytherapy and chemotherapy for unresectable recurrent breast cancer

“…[ 21 ] Similar biological effects were found in pancreatic, gastric, and lung cancer cell lines. [ 22 – 24 ] The basic research provided evidence for clinical application of 125 I radioactive seeds. The available irradiation range of 125 I radioactive particles used in our study is 1.7 cm, and the average energy is 27 to 32 keV, so it is easy to protection, clinical application are safe.…”