[en] Glioblastoma constitute the most frequent and deadliest type of brain tumors in human adults.
They are very resistant to all current therapies and are associated with a huge rate of
recurrence. In most cases, this type of tumor is characterized by a constitutive activation of
the nuclear factor-kappaB (NF-kappaB). This factor is known to be a key regulator of various
physiological processes such as inflammation, immune response, cell growth or apoptosis. In
the present study, we explored the role of NF-kappaB activation in the sensitivity of human
glioblastoma cells to a treatment by 5-aminolevulinic acid (5-ALA)–based photodynamic
therapy (PDT). Our results show that inhibition of NF-kappaB improves glioblastoma cell
death in response to 5-ALA-PDT. We then studied the molecular mechanisms underlying the
cell death induced by PDT combined or not with NF-kappaB inhibition. We found that PDT
mainly induced necrosis in glioblastoma cells and NF-kappaB was found to have anti-necrotic
functions in this context. In the second part of this study, we examined the role of the kinase
RIP3, recently identified as a key effector of the necrotic pathway, in 5-ALA-PDT-induced
necrosis and studied whether NF-kappaB interfered in RIP3-dependent necrosis induction.
