Dihydroartemisinin enhances sensitivity of nasopharyngeal carcinoma HNE1/DDP cells to cisplatin-induced apoptosis by promoting ROS production
10.12122/j.issn.1673-4254.2024.08.14
- VernacularTitle:双氢青蒿素通过促进活性氧的产生增强鼻咽癌细胞对顺铂诱导凋亡的敏感性
- Author:
Xiaofan CONG
1
;
Teng CHEN
;
Shuo LI
;
Yuanyuan WANG
;
Longyun ZHOU
;
Xiaolong LI
;
Pei ZHANG
;
Xiaojin SUN
;
Surong ZHAO
Author Information
1. 蚌埠医科大学药学院//安徽省生化药物工程技术研究中心,安徽 蚌埠 233030
- Keywords:
nasopharyngeal carcinoma;
dihydroartemisinin;
cisplatin;
reactive oxygen species;
proliferation;
apoptosis
- From:
Journal of Southern Medical University
2024;44(8):1553-1560
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of dihydroartemisinin(DHA)for enhancing the inhibitory effect of cisplatin(DDP)on DDP-resistant nasopharyngeal carcinoma cell line HNE1/DDP and explore the mechanism.Methods CCK-8 method was used to assess the survival rate of HNE1/DDP cells treated with DHA(0,5,10,20,40,80,and 160 μmol/L)and DDP(0,4,8,16,32,64,128 μmol/L)for 24 or 48 h,and the combination index of DHA and DDP was calculated using Compusyn software.HNE1/DDP cells treated with DHA,DDP,or their combination for 24 h were examined for cell viability,proliferation and colony formation ability using CCK-8,EdU and colony-forming assays.Flow cytometry was used to detect cell apoptosis and intracellular reactive oxygen species(ROS).The expression levels of apoptosis-related proteins cleaved PARP,cleaved caspase-9 and cleaved caspase-3 were detected by Western blotting.The effects of N-acetyl-cysteine(a ROS inhibitor)on proliferation and apoptosis of HNE1/DDP cells with combined treatment with DHA and DDP were analyzed.Results Different concentrations of DHA and DDP alone both significantly inhibited the viability of HNE1/DDP cells.The combination index of DHA(5 μmol/L)combined with DDP(8,16,32,64,128 μmol/L)were all below 1.Compared with DHA or DDP alone,their combined treatment more potently decreased the cell viability,colony-forming ability and the number of EdU-positive cells,and significantly increased the apoptotic rate,intracellular ROS level,and the expression levels of cleaved PARP,cleaved caspase-9 and cleaved caspase-3 in HNE1/DDP cells.N-acetyl-cysteine pretreatment obviously attenuated the inhibitory effect on proliferation and apoptosis-inducing effect of DHA combined with DDP in HNE1/DDP cells(P<0.01).Conclusion DHA enhances the growth-inhibitory and apoptosis-inducing effect of DDP on HNE1/DDP cells possibly by promoting accumulation of intracellular ROS.
