Adenovirus-mediated wild-type p53 expression induces apoptosis and suppresses tumorigenesis of experimental intracranial human malignant glioma

Adenoviral-mediated gene transfer for the treatment of experimental intrins ic malignant brain neoplasms holds promise. The role, however, of intracell ular, 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 resulta nt effect upon U251 human malignant glioma cellular proliferation. We furth er measured the survival of nude mice after intracranial injection of the i nfected vs. control U251 cells. The growth of the infected U251 cells was i nhibited 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 inje ctions of the U251 cells infected with the control (AdCMV.Null) vector show ed diminished survival. In contrast, mice having intracranial injections of the cells infected with the AdCMV.p53 vector showed 100% survivorship meas ured 100 days after treatment. Gene therapy via the AdCMV.p53 viral vector holds promise for the clinical treatment of human malignant gliomas.