Tp53-gene transfer induces hypersensitivity to low doses of X-rays in glioblastoma cells: a strategy to convert a radio-resistant phenotype into a radiosensitive one.
Tp53 is frequently mutated or inactivated in glioblastomas. Due to the impairment of p53 activity, glioblastomas show a high degree of radioresistance. In an attempt to convert the radioresistant phenotype to a more radiosensitive one, we evaluated the efficacy of the combination of Adp53 gene transfer and X-ray irradiation. The combination of Adp53, at low multiplicity in order to mimic the low in vivo efficiency of virus-mediated gene delivery, with X-ray irradiation resulted in a marked decrease of glioblastoms cell survival. Interestingly, Adp53 was able to induce low dose (<2Gy) hypersensitivity. The data suggest the possibility for the development of new therapeutic strategies.
D'Avenia
Paola
P
Department of Experimental Oncology, Molecular Oncogenesis Laboratory, Regina Elena Cancer Institute, Via delle Messi d'Oro 156, 00158 Rome, Italy.
Porrello
Alessandro
A
Berardo
Marco
M
Angelo
Marco D'
MD
Soddu
Silvia
S
Arcangeli
Giorgio
G
Sacchi
Ada
A
D'Orazi
Gabriella
G
D000256:Adenoviridae; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology; D002470:Cell Survival; D018014:Gene Transfer Techniques; D016158:Genes, p53; D015316:Genetic Therapy; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D010641:Phenotype; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D014964:X-Ray Therapy