:: Volume 19, Issue 3 (7-2021) ::
Int J Radiat Res 2021, 19(3): 495-503 Back to browse issues page
Targeting platelet/endothelial cell adhesion molecule 1 enhances cisplatin sensitivity of human nasopharyngeal carcinoma cells exposed to ionizing radiation
M. Xie, M. Zhao, J.S. Wang, Y.W. Zhao, Z.X. Jiang, R.Y. Wang
Department of Oncology, Zhong-Shan Hospital, Dalian University Liaoning, China , drwangry@outlook.com
Abstract:   (833 Views)
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.
Keywords: Drug resistance, ionizing radiation, MDR1, nasopharyngeal carcinoma, PECAM-1.
Full-Text [PDF 2163 kb]   (376 Downloads)    
Type of Study: Original Research | Subject: Radiobiology

XML     Print

Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Volume 19, Issue 3 (7-2021) Back to browse issues page