ABSTRACT
Objective To investigate the effect and underlying mechanism of radioactive 125I seed implantation on the angiogenesis of transplanted human lung adenocarcinoma in nude mice.Methods An animal model of transplantd human lung adenocarcinoma was established by subcutaneous implanting A549 cells into nude mice.Twenty four tumor-bearing nude mice were randomly divided into 4 groups with different irradiation doses of blank control (without any treatment) and 0 MBq,22.2 MBq,29.6 MBq and by embedding radioactive 125I seeds with an 18 G implant needle.Tumor volumes were measured every 4 days until all mice were terminated 30 d later and the tumor growth curve was drawn.The microvessel density (MVD) in the tumor tissue was detected by immunohistochemistry S-P assay.The mRNA and protein levels of VEGF and HIF-1α of each group were detected by RT-PCR and Western blot,respectively.Results After embedding of 125I seeds,the tumor volumes of 22.2 MBq group (886 ± 97) and 29.6 MBq group (590 ± 107) were significantly smaller than those of control group (2 297 ± 149) at 54 d after administration (q =14.117,17.075,P ＜ 0.05),but there were no significant differences among 0 MBq group and control group,22.2 MBq and 29.6 MBq groups (P ＞ 0.05).The immunohistochemical CD34-positive staining demonstrated that MVD in 22.2 MBq group (522 ± 119) and 29.6 MBq group (491 ± 121) were decreased significantly compared with control group (922 ± 260) (q =4.826,5.197,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).The mRNA expressions of VEGF and HIF-1α in 22.2 MBq group (0.279±0.0659,0.370 ±0.0857) and 29.6 MBq group (0.215 ±0.0620,0.278 ±0.0651) were significantly lower than those in the control group (q VEGFmRNA =18.881,17.211,q HIF-1αmRNA =15.376,14.733,P ＜0.05),but there were no significant differences among 0 MBq and control groups,22.2 MBq and 29.6 MBq groups(P ＞0.05).At the same time,the expression levels of VEGF and HIF-1α protein after 125I seed implantation were also obviously decreased in 22.2 MBq and 29.6 MBq groups (qvEGr =5.848,6.263,q HIF-1α =6.560,7.576,P ＜ 0.05),and no significant difference between 0 MBq and control groups(P ＞ 0.05) and between 22.2 MBq and 29.6 MBq groups (P ＞ 0.05).Conclusions Interstitial implantation with 125I seeds may potently inhibit angiogenesis in human lung adenocarcinoma xenografts of nude mice.