肝癌裸鼠移植瘤端粒酶活性表达的近日节律

Circadian Rhythms of DNA Synthesis and Telomerase Expression in Hepatic Cancer Transplanted in Nude Mice.

目的探讨肝癌裸鼠移植瘤细胞DNA合成与端粒酶表达的近日节律。方法在时辰同步化裸鼠中构建肝癌细胞SMMC 772 1裸鼠移植瘤 ,继续在程控光照条件下饲养 ,于光照后 3、9、1 5、2 1h取样 ,用流式细胞仪测定各时期细胞DNA含量 ,细胞周期分布及端粒酶活性水平。结果肝癌裸鼠移植瘤细胞DNA合成随近日节律变化 ,且伴随端粒酶活性的同步节律变化 ,呈近日节律特征。结论肝癌裸鼠移植瘤的生长与端粒酶活性表达在静止相达高峰 。

Objective To study the circadian rhythms of DNA synthesis and telomerase expression in hepatic cancer transplanted in nude mice Method Sixteen BALB/C mice were synchronized with an alternative lighting regimen with 12 h for light and 12 h for darkness (12:12 LD) for 4 weeks. Hepatic cancer cells (SMMC 7721) were implanted into both flanks of each mouse. One week after transplantation, sampling from the tumor was conducted at 3, 9, 15 and 21 h after light onset (HALO). Single cell suspension was obtained and stained with propidium iodide. The cellular DNA content was measured by flow cytometry. Telomerase activity was measured by PCR ELISA assay. Data were documented by ANOVA and Cosinor analysis. Result The proportion of tumor cells in phase G1,S, G2/M and telomerase activity varied according to circadian time with statistical significance, and the telomerase activity showed a synchronized variation. The distribution curves of both phase S and the expression level of telomerase were fit for Cosinor changes. Conclusion DNA systhesis and telomerase expression of SMMC 7721 cells transplanted into the nude mice varies according to the circadian rhythm. The results provide a guidance for laying down the chemotherapy protocol for human tumors, especially when the telomerase inhibitor was used as the anti cancer agent.