重组腺病毒载体介导血管抑素基因治疗大鼠脑胶质瘤的实验研究

Adenovirus mediated angiostatin gene therapy for rat glioma.

目的 研究以重组缺陷型腺病毒为载体的血管抑素基因治疗脑胶质瘤。方法 RT PCR法克隆angiostatin基因 ,构建携带血管抑素 (angiostatin)基因的重组腺病毒载体 ,体外检测angio statin的重组腺病毒载体对内皮细胞生长的抑制作用。建立皮下及脑胶质瘤大鼠模型 ,给予体内基因治疗。结果 克隆得到约 1 1Kb的angiostatin基因。构建重组腺病毒载体AdhCMV AGS ,体外试验表明 ,可以强烈抑制内皮细胞的生长。体内试验表明重组腺病毒可以在体内有效表达Angiostatin ,并且有效抑制胶质瘤的生长 ,使荷脑胶质瘤大鼠存活 90天以上。结论 以重组腺病毒为载体的血管抑素基因治疗脑胶质瘤效果显著 。

Objective To study the therapeatic effectiveness C6 glioma the recombinant adenovirus carrying angiostatin gene(AdhCMV AGS).Methods Angiostatin gene was cloned into adenovirus vector to make AdhCMV AGS, the infecting effect of AdhCMV AGS on endothelial cells(ECV304)was detected in vitros. C6 brain glioma modelin rat was established and the therapeutic effects of AdhCMV on glioma were observed by measarement of The survival time and tumor size. Results In vitro study showde what AdhCMV AGS could inhibit the proliferation of ECV304 cells significantly, but not C6 cells in vitro study showed that the size of tumors injected with AdhCMV AGS decreased, some of them even dissapeared while the size of tumors in control group (injected with saline solution)increased significantly. The survival time of AdhCMV AGS, Ad null and control group were 90 days, 16 8±2 5 days and 16 7±2 5 days respectively(P<0 01),Conclusions AdhCMV AGS could inhibit the proliferation of endothelial cells and the angiogenesis of tumor to eradicate C6 glioma. It will be a promising way for treating tumors with abundant capillary.