Objective  To study different treatment sequences by observing the radiosensitizing effect on transplanted tumors and to provide proof for clinical practice.

  Methods  Lung adenocarcinoma xenografts were used in nude mice models, and the changes in xenograft sizes were measured.All mice with average tumor volumes of 200 mm ₃ to 300 mm_? were randomized into six groups(n =5). Endostatin(ES) was administered to A549 lung cancer cells in three different ways, namely, before irradiation(methodⅠ).upon irradiation (methodⅡ).and after irradiation(methodⅢ), to establish the radiosensitizing effects.The ES-treated groups were given 20 mg-kg-1 of ES daily via subcutaneous injection for 14 days.The control group(Group A) was given an equivalence of normal sodium for 14 days.The radiotherapy group(Group B) was exposed to 20 Gy / 10 f X-ray irradiation for 14 days, at 1f/d and 5f/w.Group C was treated with ES alone at the abovementioned dosage via subcutaneous injection.Groups D, E.and F.were given ES via subcutaneous injection before, during, and after irradiation, respectively, and exposed to 20Gy/10f X-ray irradiation at lf/d and 5f/w.Treatment was conducted daily for 14 days.Then, 15 and 29 days after the treatment, the mice were sacrificed and the tumor tissues were obtained. The tissues were used in immunohistochemieal staining for CD31, MMP- 2 and vascular endothelial growth factor(VEGF).

  Results  The growth of the lung adenocarcinoma xenografts of the mice was significantly inhibited by the combined therapy and irradiation. The tumor weight in Group E as lower compared with that of any other group at 15 or 29 days after the treatment.The inhibition rate was also the highest in Group E.The capillary density and MMP - 2 and VEGF expression levels degraded in all groups with ES treatment.Immunohistochemical assay showed positive VEGF expression in the tumors of each group, as well as the differences between the treatment and control groups(P < 0.05).

  Conclusion  In this study, the inhibitory action in the groups treated with ES and exposed to irradiation was superior compared with those of the groups exposed to radiotherapy alone or simple ES therapy.In particular, the group treated with ES and exposed to irradiation had the optimal radiosensitizing effect compared with all other groups.