Study on the effect of down-regulating SMAD2/3 expression on the sensitivity of nasopharyngeal carcinoma cells to radiotherapy and chemotherapy
10.16066/j.1672-7002.2024.12.001
- VernacularTitle:下调SMAD2/3表达对鼻咽癌细胞放疗和化疗敏感性的影响研究
- Author:
Ying HU
1
;
Wei LE
;
Shengwei ZHANG
;
Zheng CHENG
;
Xiaoli LI
;
Qingjie CHEN
Author Information
1. 咸宁市中心医院,湖北科技学院附属第一医院肿瘤科,湖北 咸宁 437000
- Keywords:
Nasopharyngeal Carcinoma;
Transcription Factors;
Consolidation Chemotherapy;
radiotherapy;
SMAD2;
SMAD3;
PI3K
- From:
Chinese Archives of Otolaryngology-Head and Neck Surgery
2024;31(12):749-754
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To explore the effects of SMAD2/3 expression on radiotherapy and chemotherapy sensitivity in nasopharyngeal carcinoma(NPC)cells.METHODS The expression of SMAD2/3 was detected by immunofluorescence staining in the tissues of NPC,Western blot and qRT-PCR were used to detect the expression of SMAD2/3 in four human NPC cell lines(CNE-2,5-8F,Hone1,HK-1)and two human normal nasopharyngeal epithelial cells(HNEpC,NP69).The CNE-2 cell line(shSMAD2/3)and its control cell line(shSMAD2/3-NC)were constructed by lentiviral transfection.The transfected cells were treated with 4 Gy irradiation,10 μmol/L cisplatin chemotherapy and 4 Gy irradiation plus 10 μmol/L cisplatin chemotherapy respectively.The cell proliferation activity was detected by colony formation assay,the ability of cell migration was detected by scratch test,the ability of cell invasion was detected by Transwell test,and the phosphorylation level of PI3K/AKT/mTOR pathway was detected by Western blot.Then,PI3K agonist 740 Y-P was added to the experiment.RESULTS SMA2D/3 were highly expressed in NPC tissues and cell lines(all P<0.05).Compared with shSMAD2/3-NC cells,shSMAD2/3 cells were more sensitive to radiotherapy and chemotherapy,and their proliferation,migration and invasion were significantly inhibited(all P<0.05).The phosphorylation of PI3K/AKT/mTOR pathway was significantly decreased in shSMAD2/3 cells(all P<0.05).740 Y-P significantly increased the phosphorylation levels of the PI3K/AKT/mTOR pathway in the shSMAD2/3 group cells,effectively reversing the inhibition of cell viability by SMAD2/3 knockdown,and reducing the sensitivity of cells to radiotherapy and chemotherapy(all P<0.05).CONCLUSION SMAD2/3 is highly expressed in nasopharyngeal carcinoma,and down-regulation of SMAD2/3 expression increases the of nasopharyngeal carcinoma cell lines to radiotherapy and chemotherapy by reducing the phosphorylation levels of the PI3K/AKT/mTOR pathway.
