中国耳鼻咽喉头颈外科2025，Vol.32Issue(8)：518-524,7.DOI:10.16066/j.1672-7002.2025.08.009
褪黑素促进头颈鳞状细胞癌中阿霉素介导细胞凋亡的机制研究
Study on the mechanism by which melatonin enhances doxorubicin-mediated apoptosis in head and neck squamous cell carcinoma
摘要
Abstract
OBJECTIVE Melatonin(MEL),a natural hormone with broad-spectrum anticancer effects,has been shown to potentiate the therapeutic outcomes of conventional chemotherapy.This study aims to investigate the combined effects of Doxorubicin(DOX)and MEL on head and neck squamous cell carcinoma(HNSCC)cell lines.METHODS The effects of MEL and DOX on cell proliferation in HNSCC cell lines TU686 and CAL-27 were assessed using the MTT assay.The effects of MEL and DOX on reactive oxygen species(ROS)expression levels in HNSCC cell lines were detected using DCFH-DA fluorescent probe.The effects of MEL and DOX on 8-hydroxy-2′-deoxyguanosine(8-oxodG)levels in HNSCC cell lines were measured by enzyme-linked immunosorbent assay(ELISA).The effects of MEL and DOX on γ-H2AX protein levels in HNSCC cell lines were analyzed via Western blot.The effects of MEL and DOX on antioxidant enzymes levels in HNSCC cell lines were evaluated based on spectrophotometry.The effects of MEL and DOX on cell apoptosis in HNSCC cell lines were detected using an ELISA cell death detection kit.RESULTS The MTT assay revealed that MEL significantly enhanced the cytotoxic effects of DOX in HNSCC cell lines(tTU686=13.51,tCAL-27=17.580,all P<0.05).The combination of MEL and DOX markedly increased intracellular ROS levels(FTU686=89.984,FCAL-27=102.853,all P<0.05),while the expression of antioxidant enzymes was significantly reduced(TU686:the F values of CAT,GPx,GR,GST and SOD are 176.035,34.662,20.260,120.105 and 184.254,all P<0.05;CAL-27:the F values are 96.801,177.398,97.849,102.750 and 186.608 respectively,all P<0.05).Furthermore,this combination treatment significantly elevated the expression levels of 8-oxodG(FTU686=200.078,FCAL-27=663.982,all P<0.05)and γ-H2AX(FTU686=192.500,FCAL-27=285.700,all P<0.01)in HNSCC cell lines.Additionally,compared to single-agent treatment,MEL significantly enhanced DOX-induced apoptosis in HNSCC cell lines(FTU686=2718.253,FCAL-27=5185.334,all P<0.01).CONCLUSION The combination of MEL and DOX can enhance cytotoxic effects on HNSCC cell lines,increase intracellular ROS levels,induce DNA oxidative damage,and impair cellular antioxidant defense capacity,thereby effectively promoting HNSCC cell apoptosis.This combination may represent a novel therapeutic approach to improve clinical outcomes in HNSCC.关键词
头颈鳞状细胞癌/细胞凋亡/褪黑素/阿霉素/氧化DNA损伤Key words
Squamous Cell Carcinoma of Head and Neck/Apoptosis/melatonin/doxorubicin/oxidative DNA damage引用本文复制引用
王爽,崔捷,魏明辉,朱伟谕..褪黑素促进头颈鳞状细胞癌中阿霉素介导细胞凋亡的机制研究[J].中国耳鼻咽喉头颈外科,2025,32(8):518-524,7.基金项目
深圳市科技计划资助(JCYJ20230807141100001) （JCYJ20230807141100001）
湖南省自然科学基金(2022JJ40712) （2022JJ40712）
