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Radiation‐induced expression of functional Fas ligand in EBV‐positive human nasopharyngeal carcinoma cells

Ionizing radiation remains a major therapeutic tool against human cancers, especially epithelial tumors, which account for the majority of human malignancies. Although Fas and Fas‐L are essential determinants of apoptosis, few data support their role in the cytotoxic effect of ionizing radiation. Epstein‐Barr‐virus (EBV)‐positive nasopharyngeal carcinoma (NPC) were chosen to address this question owing to their known sensitivity to ionizing radiation and their constitutive expression of the Fas‐receptor. We here report that, in xenografted NPC cells, Fas‐L expression, which was very low in basal conditions, was dramatically increased by tumor irradiation. Both the Fas receptor and the Fas ligand were found to be functional in this model, and a high proportion of irradiated NPC cells underwent apoptosis following tumor irradiation. Induction of Fas‐L expression and apoptosis were observed for doses as low as 2 Gy. These data show an increase in Fas‐L expression upon irradiation exposure, and strongly suggest that, in some epithelial malignancies, Fas‐mediated apoptosis can play a major role in the anti‐tumor effect of ionizing radiation, in the range of doses used for therapeutic applications. Int. J. Cancer 86:229–237, 2000. © 2000 Wiley‐Liss, Inc.