拓扑替康对裸小鼠鼻咽癌放射增敏作用的分子水平探讨

The Investigation on Molecular Level in Radiosensitizing Effect of Topotecan of Nude Mouse with Nasopharyngeal Carcinoma in Vivo

目的:探讨拓扑替康(TPT)对鼻咽癌裸鼠移植瘤放射增敏作用的基因水平机制。方法:应用实时荧光定量RT-PCR技术检测放射增敏实验各组(TPT+RT组,TPT组,RT组,生理盐水对照组)肿瘤标本中拓扑异构酶I(拓扑异构酶-I)基因mRNA表达水平。结果:制作的定量标准曲线线性相关系数为-0.99。各组的结果为:RT+TPT组45±2.128拷贝数/μl;TPT组2112±1.208拷贝数/μl;RT20Gy组1699±1.317拷贝数/μl;生理盐水对照组3559295±1.154拷贝数/μl。TPT+RT组的拓扑异构酶-I基因mRNA表达水平最低,与TPT组,RT20Gy组比较差异有统计学意义(P<0.05);各组与生理盐水对照组比较,差异均有统计学意义(P<0.05)。结论:拓扑替康和放疗同时使用影响鼻咽癌细胞拓扑异构酶-I基因活性水平,使其下降,可能是其增敏作用在分子水平的重要机制。

Objective： To detect the molecular mechanism of radiosensitizing effect of Topotecan on Nasopharyngeal carcinoma mude mice xenografts. Methods： The real-time fluorescence quantitative RT-PCR was used to detect the active mRNA gene level of topoisomerase I in tumor specimens received from radiosensition study. Results： The linear coefficient of correlation of the quantitative standard curve was -0.99. The results in the groups were as follows： the mRNA gene level of Topo-Ⅰ was 45±2.128 copies/μl in the RT＋ TPT group （the radiosensation group）, 2112±1.208 copies/μl in the TPT group, 1699 ±1.317 copies/μl in the RT20Gy group and 3559295±1.154 copies/μl in the control group, respectively. The level of Topo-Ⅰ in RT＋ TPT group was the lowest in all the four groups. The statistical significance was shown as compared to the level of TPT group or of RT20Gy group （P〈0.05）. The statistical significance had also been shown as compared that in each groups with the controls （P〈0.05）. Conclusion： Administration of topotecan with concurrent radiotherapy can affect and decrease the level of gene activity of topoismerase in the nasopharyngeal-carcinoma ceils and this might be an important mechanism of sensitizing effect in the molecular level.