Synchrotron-based photon activation therapy effect on cisplatin pre-treated human glioma stem-like cells

Background. Glioblastoma multiforme (GBM) is one of the deadliest cancers since it shows a very limited sensitivity to chemo- and/or radiotherapy. Experimental evidence suggests that the presence in the tumour environment of GBM stem-like cells might be particularly relevant to confer this extraordinary resistance to treatment. Aim. In this study, we aimed at providing a proof-of-concept of the efficacy of Photo Activation Therapy (PAT) using monochromatic X-rays, issued from a synchrotron radiation (SR) source, in killing human glioma stem cells pre-treated with cisplatin. We have also investigated if lethality of this treatment was superior to that achievable with conventional X-ray irradiation. Material and Methods. Cisplatin was chosen as the carrier of platinum atoms in the cells based on previous experience in glioma and non-glioma cancer cells; the irradiation was performed by delivering 1-8 Grays using beams of energies just above or below the platinum K-shell edge (78.39 keV) or with a conventional X-ray source. Cells were exposed to low drug concentrations allowing 90% or more of GBM stem-like cells survival thus mimicking the unfavourable tissue distribution generally achieved in GMB patients. Results. Under these experimental conditions a significant enhancement in cell lethality was observed using SR with respect to conventional X-ray irradiation. Conclusions. Our results provide additional support to the suggestion that PAT deserves to be further explored in relevant in vivo models based on GBM stem-like cells.