Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma
Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma
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DOI：
10.1023/a:1006289505801
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发表时间：
1999-06-01
影响因子：
3.9
通讯作者：
Williams, JA
中科院分区：
文献类型：
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作者：
Cirielli, C;Inyaku, K;Williams, JA
腺病毒介导的基因转移治疗实验性脑内恶性肿瘤大有可为。然而，细胞内腺病毒介导的P53表达抑制实验性人颅内恶性胶质瘤生长的作用仍在很大程度上尚不清楚。利用AdCMV.P53载体，我们检测了P53的体外表达及其对U251人恶性胶质瘤细胞增殖的影响。我们进一步测量了感染的U251细胞与对照组U251细胞脑内注射后裸鼠的存活率。与未感染的细胞和感染对照载体(AdCMV.Null)的细胞相比，感染的U251细胞的生长受到抑制。琼脂糖凝胶电泳法证实了AdCMV.P53依赖的细胞凋亡。裸鼠脑内注射感染了对照载体(AdCMV.Null)的U251细胞后，存活率下降。相比之下，脑内注射感染了AdCMV.P53载体的细胞的小鼠在治疗100天后显示出100%的存活率。通过AdCMV.P53病毒载体进行的基因治疗有望用于人类恶性胶质瘤的临床治疗。
Adenoviral-mediated gene transfer for the treatment of experimental intrinsic malignant brain neoplasms holds promise. The role, however, of intracellular, adenoviral-mediated p53 expression to inhibit growth of experimental human intracranial malignant gliomas remains largely unexplored. Using the AdCMV.p53 vector we measured the in vitro expression of p53 and the resultant effect upon U251 human malignant glioma cellular proliferation. We further measured the survival of nude mice after intracranial injection of the infected vs. control U251 cells. The growth of the infected U251 cells was inhibited when compared to both the uninfected cells and cells infected with the control vector (AdCMV.Null). Agarose gel electrophoresis confirmed the AdCMV.p53-dependent cellular apoptosis. Nude mice having intracranial injections of the U251 cells infected with the control (AdCMV.Null) vector showed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship measured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.