International Journal of Radiation Research
نشریه پرتو پژوه
Int J Radiat Res
Basic Sciences
http://ijrr.com
79
journal79
2322-3243
2345-4229
10.61186/ijrr
en
jalali
1400
4
1
gregorian
2021
7
1
19
3
online
1
fulltext
en
Targeting platelet/endothelial cell adhesion molecule 1 enhances cisplatin sensitivity of human nasopharyngeal carcinoma cells exposed to ionizing radiation
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–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