SUPPRESSION OF CELLULAR P53 PROMOTES CYTOTOXICITY OF ONCOLYTIC VECTOR AT THE MODELS OF HUMAN GLIOBLASTOMA

Glioblastoma multiforme resistance requires a new approach for glioma therapy. Protein p53 is one of the main cellular oncogene, overexpressed in 50% of brain tumor cases. Impact of p53 attenuation was evaluated in the presence of oncolytic adenovirus and temodar, which exhibit anti-glioma effect using in vitro glioma models. Using U87 human glioma cells we observed an additive effect between alkilated chemotherapeutic agent temodar and oncolytic adenovirus which results into p53 inhibition. It occurs that attenuation of p53 using PFTa inhibitor, significantly prolongs cell death type II - autophagy and, therefore improves effect mediated by autophagy induced agents. In conclusion, combination of PFTa and temodar might represent a powerful therapeutic combination which sensibilises glioma cells to the infection with oncolytic vector.

аденовирус, P53, аутофагия, пролиферация, adenovirus, p53, autophagy, proliferation