端粒酶核酶抑制裸鼠移植瘤生长的实验研究

目的　探讨端粒酶核酶对裸鼠移植瘤生长的影响。方法　构建了人子宫颈癌细胞株HeLa 裸鼠移植瘤,将不同剂量端粒酶核酶真核表达质粒pXJ-neo-teloRZ用脂质体包裹后进行瘤体内多点注射,对照组注射生理盐水或空质粒载体。连续注射14 天,测量肿瘤体积和重量,检测瘤组织端粒酶活性,并作病理切片检查。结果　端粒酶核酶使肿瘤组织端粒酶活性下降,肿瘤组织凋亡增加,明显地抑制了裸鼠移植瘤生长。结论　该端粒酶核酶可望成为有效的端粒酶抑制剂,在肿瘤基因治疗中发挥作用。

Study on the inhibition of nude mice transplantation tumor growth by telomerase ribozyme

OBJECTIVE: To explore whether telomerase ribozyme could inhibit the growth of nude mice transplantation tumor. METHODS: A xenograft human-nude mouse model was constructed. A total of 24 mice were divided into 4 groups, namely, the saline control(Group 1), the blank plasmid control(Group 2), the 20 microg/mouse/day p(XJ-neo-teloRZ)(Group 3) and the 30 microg/mouse/day p(XJ-neo-teloRZ)(Group 4). All plasmids were packaged by lipofectamine and used for subcutaneous, continuous infusions over 14 days. Tumor measurements and observations of animal behavior were recorded daily.On completion of the study, the mice were killed by cervical dislocation and their organs were removed, weighed, and stored in formaldehyde for histological examination. The telomerase activities of tumor tissues of each group were also detected. RESULTS: The telomerase ribozyme effectively inhibited the telomerase activities of tumor tissues and promoted the apoptosis of tumor cells. The in vivo studies showed a significant decrease in tumor size in mice treated with p(XJ-neo-teloRZ) when compared to the mice treated with controls. Furthermore, the in vivo effect of p(XJ-neo-teloRZ) was dose dependent. CONCLUSION: Telomerase ribozyme is a powerful telomerase inhibition agent; probably it could be effective in tumor gene therapy.