Endostatin Combine Radiation To Cure Lung Cancer At Different Administration Times In Vivo

Objective:Conventional therapies for lung cancer have reached a therapeutic plateau. Endostatin has been demonstrated to represent a promising novel approach to the treatment of malignant tumors. Most likely, it will have to be combined with conventional treatment strategies adding to the multimodality approach to these tumors. Meanwhile, a promising area of research in radiation oncology is the integration of molecular targeting agents to improve the effectiveness of RT in achieving primary tumor control. However,it does not know the optimal time to combinate ES and radiation.So,we try to study the different treatment sequence by observing the radiosensitive effect in transplanted tumor,in order to give the prove to clinic.Methods:Using of the lung adenocarcinoma xenografts in nude mice model, measuring changes of xenografts size, All mice were randomized into 6 groups (n=5) when average volume of tumor achieved (200-300) mm3. We demonstrated that ES was administered to A549 lung cancer cells in three different ways (methodⅠ: administration before irradiation, methodⅡ:administration upon irradiation, methodⅢ:administration after irradiation) to establish the radiosensitizing effect respectively. ES group:mice were given 20 mg·kg-1 of ES daily by subcutaneous injection for 14 days.Control group:mice were given by equal volumes of normal sodium for 14 day.Radiotherapy group:mice were treated by 20Gy/10f X-ray irradiation for 14 day,1f/d,5f/w,ES plus radiotherapy group:mice were given daily by subcutaneous injection for 14 days,before or at the same time or after,administrate 20Gy/10f X-ray irradiation for 14 day,1f/d,5f/w.In 15 or 29 day after treatment,the mice were killed and tumor tissues were obtained and used for immunohistochemical staining for CD31, which is the indicator of capillary vessel density, and for MMP-2,VEGF.Results:In combination with radiotherapy for lung adenocarcinoma xenografts in nude mice model significant growth inhibition,and E group tumor weight lower than any other group in 15 or 29 day after treatment.While the inhibition rate for E group was significantly highest. The density of capillary vessel and the expression of MMP-2 and VEGF degraded in all groups with Es treatment. Immunohistochemistry test showed that expression of vascular endothelial growth factor(VEGF)were positive by tumors in each group,and there were difference between treatment groups and control group(P＜0.05).Conclusion:ES inhibitory effect of combined radiation was superior to radiotherapy alone group and simply ES group by studying lung adenocarcinoma xenografts in nude mice model,Specially,the radiatosensitive effect in administration upon irradiation group is the best. Possible mechanisms for the additive effect when combining ES with RT include direct tumor cell effects and improved tumor oxygenation through mechanisms such as elimination of ineffective tumor vessel networks In summary, a decrease in interstitial fluid pressure and endothelial cell radiosensitization.By damaging the tumor vasculature, it is possible to kill the hundreds of tumor cells fed by the target vessel. ES alone would be difficult to produce the desired blocking effect, but at the same time, the radiation injury for endothelial cells was also nonspecific. The vascular endothelial injury could be more intense, and the blood supply blocking could be more perfect when ES combined with irradiation.our study provides a beneficial exploration of optimal administration time when ES combined with radiation. Although many issues remain to be addressed, we believe that, with further development of fundamental research, application of irradiation in combination with ES in clinical practice will continue to be improved.