The Mechanism Of Chronomodulated Radiosensitization By TPT On Nasopharyngeal Carcinoma In Vivo

Abstract Objective:To investigate expressions level of Topo I in tumor tissue after the chronomodulated radiosensitization on human nasopharyngeal carcinoma(NPC) in nude mice, and to disclose the mechanism of chronomodulated radiosensitization on nasopharyngeal carcinoma.Methods: 110 Balb/c mice were synchronized with an alternative lighting regimen with 12 hours for light and 12 hours for dark at least 3 weeks. Human nasopharyngeal poorly differentiated squamous cell carcinoma(CNE-II) cells were implanted into the right lateral thigh of each mouse. Three weeks after transplantation,96 nude mice xenografts were divided into 4 groups: radiotherapy(RT) group, RT+TPT group, TPT group and control group. Each group was divided into 4 subgroups at 3HALO,9HALO,15HALO,21HALO. TPT (10mg/kg) were injected introperitoneally half-hour before four time points in RT+TPT group and RT group. RT+TPT group and RT group were given radiotherapy which dose of 18Gy at four time points. All groups mice were exceuted one hour after radiotherapy. The expressions of Topo I were detected by immunohistochemistry and were analyzed by Image-Pro Plus(IPP) software. Data were analyzed by completely randomized single-factor variance analysis method. Results:According to immunohistochemical results, the expressions Topo I have circadian rhythm. In the same time point, the expressions of Topo I had significant difference between RT+TPT group and RT group(P<0.01). In all groups, the lowest expression of Topo I is RT+TPT group, and the expression of 15HALO subgroup is minimum in all subgroups. The expression of Topo I in RT+TPT group: 15HALO<21HALO<3HALO<9HALO. There were statistical difference between 9HAL0 group and other groups(P<0.01). The expression of Topo I in RT group:21HALO<3HALO<15HAL0< 9HAL0. There were statistical difference between 21HAL0 group and 9HAL0 group(P<0.05). Conclusion: According to the result of this experiment and preliminary study, the mechanism of chronomodulated radiosensitization by TPT may be:1. The level of Topo I varies according to circadian rhythm.2. The level of Topo I varies after chronomodulated radiotherapy.