Abstract
Despite significant advances, the radiotherapy and chemotherapy protocols marginally improve the overall survival of patients with glioblastoma. LipoplatinTM, and LipoxalTM, the liposomal formulations of cisplatin and oxaliplatin respectively, were tested on the F98 glioma cells for their ability to improve the cell uptake and increase the synergic effect when combined with ionizing radiation. The cytotoxicity and synergic effect of platinum compounds were assessed by colony formation assay, while the cellular uptake was measured by Inductively Coupled Plasma Mass Spectrometer (ICP-MS). After 4 h exposure with platinum compounds, cells were irradiated (1.5–6.6 Gy) with a 60Co source. The liposomal formulations were compared to their liposome-free analogs and to carboplatin. The concomitant treatment of F98 cells with carboplatin and radiation produced the highest radiosensitizing effect (30-fold increase). Among the platinum compounds tested, LipoplatinTM produced the most promising results. This liposomal formulation of cisplatin improved the cell uptake by 3-fold, and its radiosensitizing potential was enhanced by 14-fold. Although LipoxalTM can potentially reduce the adverse effect of oxaliplatin, a synergic effect with radiation was measured only when incubated at a concentration higher than its IC50. Conversely, concomitant treatment with cisplatin did not result in a synergic effect, as in fact a radioprotective effect was measured on the F98 cells. In conclusion, among the five platinum compounds tested, carboplatin and LipoplatinTM showed the best radiosensitizing effect. LipoplatinTM seems the most promising since it led to the best cellular incorporation and has already been reported to be less neurotoxic than other platinum compounds.
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Acknowledgments
This research project was funded by the Canadian Institutes of Health Research, grant # MOP 81356. BP and LS are members of the FRSQ-funded Centre de recherche clinique Étienne-LeBel. Special thanks to REGULON, Inc. for the free supply of LipoplatinTM and LipoxalTM.
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Charest, G., Paquette, B., Fortin, D. et al. Concomitant treatment of F98 glioma cells with new liposomal platinum compounds and ionizing radiation. J Neurooncol 97, 187–193 (2010). https://doi.org/10.1007/s11060-009-0011-5
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DOI: https://doi.org/10.1007/s11060-009-0011-5