The Experimental Study Of Radiosensitization Effect Of Endostar On Transplantanted Tumor Model Of Nasopharyngeal Carcinoma In Balb/c Nude Mice

Objective: To evaluate the synthetical inhibitory effect of Endostar combined with radiotherapy on transplanted human Nasopharyngeal Carcinoma in BALB/c nude mice, and to explore the possible mechanisms and the application possibility of antiangiogenic target therapy combinated with radiotherapy.Methods: The transplanted tumor model of nasopharyngeal carcinoma on nude mice was established. When the average volume of tumor mass on nude mice was around 391.270±78.787mm3,the nude mice were divided into four groups, control,endostar,radiation and endostar+radiation,randomly.Each mouse from endostar group and combination group was injected with endostar 20mg/kg/d for ten days. Each mouse from radiation group and combination group after injection with endostar was given electron-ray radiotherapy by 20Gy once on the 10th day. Four weeks after the treatment, the mice were killed and the transplanted tumor was sampled and preserved into the liquid nitrogen. By real-time fluorescent quantitatiye PCR, the mRNA expression level of VECF, Survivin,MMP-2 and MMP-9 in tumor samples were detected, and the apoptosis conditions in tumor samples were also examined by optical microscope.Results: (1) Subcutaneous transplanted tumor models on nude mice could be established successfully after inoculation with CNE1 cells in all experimental mice,and the rate of tumor formation is 100% (2) The combination therapeutic regimen has more significant inhibition effect on the tumor growth and the tumor mass weight and volume in combination group were much smaller than other three groups, and the differences were significant (P<0.05). (3) In all groups, VEGF, Survivin,MMP-2 and MMP-9 mRNA expression could be detected at different level, while their expression level in combination group were much lower than in other three groups. (P<0.05). (4) The expression level of VECF has the positive correlation with that of Survivin, while the expression level of VEGF also has the positive correlation with that of MMP-2 and MMP-9 (P<0.01).(5) By optical microscope, tumor cells in the tumor sample from combination group were much scarce and showed a higher apoptosis rate compared with other three groups.Conclusion: (1) Endostar in combination with radiotherapy had much more obvious inhibitory effect on the growth of transplanted CNE1 Nasopharyngeal Carcinoma in BALB/c nude mice, and the inhibitory effect was superior to radiotherapy alone group and simply Endostar group, and Endostar in combination with radiotherapy could enhance the radiosensitivity of tumor cells to radiotherapy. (2) Endostar in combination with radiotherapy could inhibit the new-growing vessels of tumors and improve the apoptosis rates of tumor cells through lowering the expression level of VEGF,Survivin,MMP-2 and MMP-9,which may be one of the mechanisms of its radiosensitization effect. (3) The expression level of VEGF had a positive correlation with that of Survivin, while the expression level of VEGF also had a positive correlation with that of MMP-2 and MMP-9, which indicated that the formation of tumor vessels was a complex process, during this process a lot of genes and factors were involved.