低氧诱导因子-1α核酶基因对裸鼠胶质瘤生长的抑制作用

Study on the inhibition of nude mice transplantation tumor growth by hypoxia-induced factor-1α ribozyme

目的:探讨低氧诱导因子-1α(HIF-1α)核酶对裸鼠胶质瘤生长的影响。方法:构建鼠胶质瘤细胞株C6裸鼠移植瘤,将HIF-1α核酶真核表达质粒Psuper-Rz用脂质体包装后进行瘤体内多点注射,对照组注射PBS和空质粒载体。连续注射14d,测量肿瘤体积,检测瘤组织HIF-1α的生物活性,并作病理切片检查。结果:HIF-1α核酶使肿瘤组织HIF-1α活性下降,肿瘤组织血管生成减少,明显抑制了裸鼠移植瘤生长。结论:该核酶有望成为有效的HIF-1α抑制剂,在肿瘤基因治疗中发挥作用。

OBJECTIVE To explore whether hypoxia-induced factor-1αribozyme could inhibit the growth of nude mice transplantation tumor. METHODS A xenograft C6 nude mouse model was constructed. 45 mice were divided into 3 groups, the PBS control（Group1）, the blank plasmid control（Group2）, the 30μg/mouse/day psuper-RZ （Group3）. All plasmids were packaged by lipofectamine and used for subcutaneous, continuous infusions over 14 days. Tumor measurement of animal behavior were recorded daily. On completion of the study, the mice were killed by cervical dislocation and their organs were removed and stored in formal dehyde for histological examination and immunohistochemical staining. The Hif-1α activities of tumor tissues of each group were also detected. RESULTS The Hif-1αribozyme effectively inhibited the Hif-1αactivities of tumor tissues and inhibited the the build of vessels of tumor cells. The fn vivo studies showed a significant decrease in tumor size in mice treated with psuper-Rz when compared to the mice treated with controls. CONCLUSION Hif-la ribozyme is a powerful Hif-1α-hibhion agent; probably it could be effective in tumor gene therapy.