en Radiobiology Radiobiology تحقيق بديع Original Research <div style="text-align: justify;">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&ndash;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.</div> Drug resistance, ionizing radiation, MDR1, nasopharyngeal carcinoma, PECAM-1. 495 503 http://ijrr.com/browse.php?a_code=A-10-2188-22&slc_lang=en&sid=1 M. Xie 7900319475328460020212 7900319475328460020212 No Department of Nuclear Medicine, Zhong-Shan Hospital, Dalian University, Liaoning, China M. Zhao 7900319475328460020213 7900319475328460020213 No Department of Oncology, Zhong-Shan Hospital, Dalian University Liaoning, China J.S. Wang 7900319475328460020214 7900319475328460020214 No Graduate school, Dalian Medical University, Dalian, Liaoning, China Y.W. Zhao 7900319475328460020215 7900319475328460020215 No Graduate school, Dalian Medical University, Dalian, Liaoning, China Z.X. Jiang 7900319475328460020216 7900319475328460020216 No Department of Oncology, Sheng-Jing Hospital, China Medical University, Liaoning, China R.Y. Wang drwangry@outlook.com 7900319475328460020217 7900319475328460020217 Yes Department of Oncology, Zhong-Shan Hospital, Dalian University Liaoning, China