Radio-sensitization of chondrosarcoma cells by PARP inhibitors

International audienceChondrosarcoma is a malignant tumor arising from cartilaginous tissue and presenting radio- and chemo- resistances to conventional treatments. The main treatment first consists to a surgical resection, which may conduct to severe disabilities for the patient; in addition, this procedure may not be possible for inoperable locations such as the skull base. Carbon-ion irradiation (hadron-therapy) is proposed as an alternative treatment, due notably to a higher biological effectiveness and a better ballistic as compared with conventional radiotherapy with X-Rays. This study aimed to examine the cellular responses of chondrosarcomas to conventional radiotherapy and hadrontherapy, associated with PARP-inhibitors in order to better understand the biological effects of combined treatments. Three human chondrosarcoma cell lines of different grades and displaying differential radio-sensitivities, were irradiated with photons, proton or carbon ions, in association with different PARP inhibitors.To better understand the PARP-inhibition process, we first analyze Poly-ADP ribose chains formation using western blotting, and we observed a maximum of signal after irradiation with CH2879 cells. As attempted, clonogenic assays confirmed the better biological effectiveness of carbon ion over X-Rays; the resistance to radiation of each cell line was calculated from the corresponding survival curves. PARP-inhibitors increase radio-sensitivity, with a factor depending of the dose and irradiation quality(1). Apoptosis is increased following treatments, as observed by flow cytometry and western blotting experiments.This study demonstrates the capacity of PARP-inhibitors in radio-sensitizing chondrosarcoma cells, using conventional photon irradiation, but also, using proton beam and carbon beam irradiations