【摘要】 目的观察甘氨双唑钠(CMNa)联合时辰放疗对鼻咽癌裸鼠移植瘤的时辰放射增敏作用,并探讨其作用机制。方法将荷瘤裸鼠随机分为3组:放疗组、放疗+CMNa组、空白对照组,每组分3HALO(光照后小时,hours after light onset)、9HALO、15HALO、21HALO四个时辰进行相应处理。测定肿瘤再生长延长时间(regrowth delay time,TGD),绘制生长曲线。用免疫组化法检测各组肿瘤标本中HIF-1α、γ-H2AX和凋亡蛋白的表达。结果通过对各组TGD的比较,以放疗+CMNa组对肿瘤的抑制效果最好。在该组中,TGD:15HALO>21HALO>9HALO>3HALO,15HALO与3HALO的TGD比较有统计学意义;15HALO与3HALO的HIF-1 α、γ-H2AX及凋亡蛋白的表达水平比较有统计学意义。结论甘氨双唑钠联合时辰放疗对鼻咽癌裸鼠移植瘤有明显的时辰放射增敏作用,以15HALO放疗+CMNa组对肿瘤的抑制效果最佳。其机制可能与HIF-1α的表达,DNA双链损伤,凋亡有关。更多还原

【Abstract】 Objective: To investigate the chronomodulated radiosensitization by CMNa on human nasopharyngeal carcinoma( NPC) in nude mice and to disclose its mechanism.Method: Nude mice xenografts were divided into 3 groups: radiotherapy ( RT) group, RT + CMNa group and control group.Each group was respectively dealt with at 3HAL0,9HALO, 15HALO, 21 HALO.After treatment, regrowth delay time (TGD) were determined and the growth curve was drawn.The expressions of HIF-1α,γ-H2AX and apoptosis proteins were detected by immunohistochemistry. Result : According to TGD, RT + CMNa group obtained the best inhibitory action of tumor.In this group, TGD had statistical difference between 15HALO and 3HALO.The expressions of HIF-1α,γ-H2AX and apoptosis proteins had significant difference between 15HALO and 3HALO.Conclusion:This study showed that CMNa combined with chronomodulated radiotherapy could obviously enhance the radiosentivity of NPC xenografts,and RT + CMNa group at 15HALO can get the greatest efficacy.Its mechanism might be related to the expression of HIF-1α,the injury of DNA double strands and apoptosis.更多还原