RESUMO
Rat glioma cell line C6 expressing human poliovirus receptor (PVR) and susceptible to polioviruses (C6-PVR-BFP) was used to produce a clone with knockout of IFNα/ß (Ifnar1) receptor subunit 1 gene (Ifnar1). The sensitivity of C6-PVR-BFP cells to the vaccine strain of poliovirus type 3 (PV3) depended on the signaling pathways of the cell response to type 1 IFN. Using the model of subcutaneous tumor xenografts, we demonstrated oncolytic activity of PV3 against C6-PVR-BFP cells that depended on the expression of PVR and increased considerably upon disturbances in IFN response pathways.
Assuntos
Glioma/terapia , Glioma/virologia , Terapia Viral Oncolítica/métodos , Poliovirus/fisiologia , Animais , Linhagem Celular Tumoral , Glioma/metabolismo , Interferon-alfa/genética , Interferon beta/genética , Camundongos , Vírus Oncolíticos/fisiologia , Ratos , Ratos Mutantes , Receptor de Interferon alfa e beta/genética , Receptor de Interferon alfa e beta/metabolismoRESUMO
The p53 tumor suppressor serves to secure genetic stability of multicellular organisms. It suppresses the accumulation of mutations in somatic cells and substantially decreases the probability of malignant diseases. The p53 gene acts highly selectively through multiple mechanisms. Under relatively favorable conditions, p53 helps to maintain intracellular homeostasis by balancing anabolic and catabolic processes and by timely elimination of reactive oxygen species. These functions of p53 facilitate maximal efficiency and survival of cells under conditions of physiological stresses. In the case of grave molecular damage caused by severe stress, a significant amount of highly active p53 is induced leading to irreversible growth arrest and programmed cell death. The induced functions of p53 secure the timely elimination from the organism of damaged and potentially dangerous cells. Collectively, the functions of p53 contribute to the prevention of malignant and other diseases and decelerate the aging process.