Targeting platelet/endothelial cell adhesion molecule 1 enhances cisplatin sensitivity of human nasopharyngeal carcinoma cells exposed to ionizing radiation

Background: cancer cells develop multidrug resistance after receiving fractionated ionizing radiation. however, the mechanisms underlying this phenomenon remain unknown. this study aimed to investigate the role of platelet/endothelial cell adhesion molecule 1 (pecam-1), which was induced by ionizing radiation, in overcoming cisplatin resistance of nasopharyngeal carcinoma (npc) cells. materials and methods: human npc cell line cne1 was subjected to fractionated ionizing radiation to obtain a subline with the phenotype of multidrug resistance (designated as cne1/r). pecam-1 gene expression in cne1/r cells was knocked down by stable transfection of psilencer plasmid carrying specific small hairpin rna. the transcripts of pecam-1 and multidrug resistance gene 1 (mdr1) were analyzed by reverse transcription–polymerase chain reaction, and their encoding proteins were detected by western blot analysis. the in-vitro viability of tumor cells was examined with mtt assay and flow cytometry analysis. the tumor growth in xenograft mice was determined by measuring tumor weights. results: the transcript and protein levels of pecam-1 and mdr1 were concomitantly upregulated in cne1 cells subjected to ionizing radiation. the inhibition of pecam-1 expression with small hairpin rna reduced the levels of mdr1 transcript and its encoding protein, p- glycoprotein. furthermore, targeting pecam-1 not only enhanced the sensitivity of irradiated cne1 cells to cisplatin-mediated cell cytotoxicity in-vitro but also resulted in tumor regression in-vivo. conclusions: an increased pecam-1 level in cne1 cancer cells subjected to ionizing radiation contributed to cisplatin resistance via the upregulation of mdr1 expression. thus, targeting pecam-1 might help overcome drug resistance induced by ionizing radiation in cne1 npc cells.