铜离子激活MAPK-ERK通路调控鼻咽癌放射敏感性

doi:10.3969/j.issn.1006-5725.2024.09.003

Abstract

Abstract:

Objective To Investigate the effect of copper ions on the radiosensitivity of nasopharyngeal carcinoma （NPC） and identify potential targets to improve the efficacy of NPC radiation therapy. Methods The content of copper ions in normal nasopharyngeal epithelial cell line NP69 and a variety of NPC cell lines was detected by a copper microplate assay. After adding 0， 5， 10， 20， 50， 100， 200 μmol/L copper ion solution and 0， 0.05， 0.1， 0.2， 0.5， 1.0， 2.0 mmol/L TEPA solution， CCK?8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation. And determine the drug concentration to be used in subsequent experiments. CCK?8 assay was used to determine the effect of intracellular copper ion content on the survival rate of NPC cells before and after irradiation， and to determine the drug concentration used in the copper ion group and TEPA group in the subsequent experiments. CCK?8 assay and clone formation assay were used to detect the changes in radiosensitivity of NPC cells after drug treatment. The DNA damage and MAPK-ERK signaling pathway-related protein expression of NPC cells in each group before and after irradiation were detected by Western blot. Results The content of copper ions in NPC cells was significantly higher than that in normal nasopharyngeal epithelial cells （P < 0.05）. When the concentration of copper ion solution was lower than 50 μmol/L， the radiation resistance of CNE1 cells was improved， and the radiation sensitivity of SUNE1 cells was increased by 0.1 ~ 0.2 mmol/L TEPA （P < 0.05）. Compared with the control group， the NPC cell radiotherapy resistance of copper ion group was enhanced， and the NPC cell radiotherapy sensitivity of copper ion group was enhanced （P < 0.05）. Compared with the control group， the activation degree of MAPK-ERK pathway in copper ion group was up-regulated （P < 0.05）. MAPK-ERK pathway inhibitor SCH772984 effectively reversed copper-mediated NPC radiotherapy resistance （P < 0.05）. Conclusion The increased copper ion content in NPC cells promoted the radiotherapy resistance of NPC cells by activating the MAPK-ERK signaling pathway.

Key words: nasopharyngeal carcinoma, copper ion, MAPK - ERK signaling pathway, radiation therapy

CLC Number:

R739.6

Xiuting HUANG,Jie LIN,Xiaoxin YE,Jiazuo CAI,Yawei. YUAN. Copper regulates the radiosensitivity of nasopharyngeal carcinoma by activating MAPK-ERK signaling pathway[J]. The Journal of Practical Medicine, 2024, 40(9): 1191-1196.

Figures/Tables 7

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References 38

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细胞	Cu²⁺含量	P值
NP69	1.07 ± 0.11
CNE1	1.57 ± 0.14	0.016
5-8F	1.77 ± 0.17	0.001
CNE2	2.07 ± 0.16	< 0.001
HONE1	2.78 ± 0.17	< 0.001
SUNE1	3.48 ± 0.24	< 0.001

Cu²⁺浓度（μmol/L）	细胞存活率		P值^#	P值^*
Cu²⁺浓度（μmol/L）	未放射	5Gy放射	P值^#	P值^*
0	100.00 ± 3.93	40.41 ± 3.48
5	99.00 ± 5.47	52.56 ± 2.24	0.999	< 0.001
10	96.79 ± 4.75	63.91 ± 1.87	0.653	< 0.001
20	98.78 ± 6.27	67.80 ± 2.96	0.999	< 0.001
50	86.99 ± 2.21	51.84 ± 2.84	< 0.001	< 0.001
100	62.13 ± 4.09	29.92 ± 1.13	< 0.001	< 0.001
200	33.35 ± 4.24	13.05 ± 1.01	< 0.001	< 0.001

TEPA浓度（mmol/L）	细胞存活率		P值^#	P值^*
TEPA浓度（mmol/L）	未放射	5Gy放射	P值^#	P值^*
0	100.00 ± 3.26	61.78 ± 4.40
0.05	102.70 ± 3.72	58.20 ± 2.10	0.856	0.193
0.10	101.80 ± 1.94	50.89 ± 2.96	0.976	< 0.001
0.20	99.57 ± 4.73	41.57 ± 2.77	1.000	< 0.001
0.50	82.37 ± 9.66	31.30 ± 3.48	< 0.001	< 0.001
1.00	77.64 ± 3.52	26.09 ± 2.68	< 0.001	< 0.001
2.00	66.12 ± 4.43	22.48 ± 2.08	< 0.001	< 0.001

组别	细胞存活率
组别	未放射	5 Gy放射
Cu²⁺组	100.00 ± 2.66	69.56 ± 2.47
Cu²⁺+SCH772984组	99.94 ± 3.78	45.12 ± 3.83
t值	0.03	3.14
P值	0.977	< 0.001

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Copper regulates the radiosensitivity of nasopharyngeal carcinoma by activating MAPK-ERK signaling pathway

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