探讨着丝粒蛋白N（CENP-N）对鼻咽癌（NPC）细胞放射敏感性的影响。采用免疫组化和免疫荧光技术检测35例放射敏感性或放射抵抗性鼻咽癌患者组织中CENP-N的表达。通过 CCK-8、集落形成、流式细胞术和蛋白质印迹评估联合 CENP-N 敲低和放射治疗对各种细胞过程的影响。建立鼻咽癌异种移植模型。当肿瘤体积达到100 mm3时，给予6 Gy的照射剂量，并使用免疫荧光和Western blotting技术在体内评估联合治疗的效果。鼻咽癌放射敏感组织中CENP-N的水平显着降低（ p < 0.05）。 CENP-N 的敲低增强了 NPC 放射敏感性，导致敏化增强比 (SER) 为 1.44 (5-8 F) 和 1.16 (CNE-2Z)。与单独的 CENP-N 敲低或单独的放疗相比，联合治疗显示出显着更高水平的增殖抑制、细胞凋亡和 G2/M 期阻滞 (p<0.01)。联合治疗组的 Bax 和 γH2AX 蛋白水平增加最多，而 Cyclin D1 蛋白水平下降最多 (p<0.01)。然而，用AKT激活剂SC79治疗后，上述变化被逆转。在体内，放疗组肿瘤的平均体积和重量分别为182±54 mm3和0.16±0.03 g。联合治疗组的平均肿瘤体积和重量分别为 84±42 mm3 和 0.04±0.01 g。敲低 CENP-N 可以通过抑制 AKT/mTOR 来增强 NPC 放射敏感性。© 2023。作者。

Investigating the impact of centromere protein N (CENP-N) on radiosensitivity of nasopharyngeal carcinoma (NPC) cells.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.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.Knockdown of CENP-N can enhance NPC radiosensitivity by inhibiting AKT/mTOR.© 2023. The Author(s).