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Journal of Translational Medicine

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Open Access 01-12-2023 | Radiotherapy | Research

Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown

Authors: Li-Zhi Wu, You Zou, Bin-Ru Wang, Hai-Feng Ni, Yong-Gang Kong, Qing-Quan Hua, Shi-Ming Chen

Published in: Journal of Translational Medicine | Issue 1/2023

Abstract

Objective

Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells.

Methods

Using immunohistochemistry and immunofluorescence to detect CENP-N expression in tissues from 35 patients with radiosensitive or radioresistant NPC. Assessing the effect of combined CENP-N knockdown and radiotherapy on various cellular processes by CCK-8, colony formation, flow cytometry, and Western blotting. Establishing a NPC xenograft model. When the tumor volume reached 100 mm³, a irradiation dose of 6 Gy was given, and the effects of the combined treatment were evaluated in vivo using immunofluorescence and Western blotting techniques.

Results

The level of CENP-N was significantly reduced in radiosensitive tissues of NPC (p < 0.05). Knockdown of CENP-N enhanced NPC radiosensitivity, resulting in sensitizing enhancement ratios (SER) of 1.44 (5-8 F) and 1.16 (CNE-2Z). The combined treatment showed significantly higher levels of proliferation suppression, apoptosis, and G2/M phase arrest (p < 0.01) compared to either CENP-N knockdown alone or radiotherapy alone. The combined treatment group showed the highest increase in Bax and γH2AX protein levels, whereas the protein Cyclin D1 exhibited the greatest decrease (p < 0.01). However, the above changes were reversed after treatment with AKT activator SC79. In vivo, the mean volume and weight of tumors in the radiotherapy group were 182 ± 54 mm³ and 0.16 ± 0.03 g. The mean tumor volume and weight in the combined treatment group were 84 ± 42 mm³ and 0.04 ± 0.01 g.

Conclusion

Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.

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Title: Enhancing nasopharyngeal carcinoma cell radiosensitivity by suppressing AKT/mTOR via CENP-N knockdown
Authors: Li-Zhi Wu
You Zou
Bin-Ru Wang
Hai-Feng Ni
Yong-Gang Kong
Qing-Quan Hua
Shi-Ming Chen
Publication date: 01-12-2023
Publisher: BioMed Central
Keyword: Radiotherapy
Published in: Journal of Translational Medicine / Issue 1/2023
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-023-04654-x

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