中国药理学通报2024，Vol.40Issue(1)：114-125,12.DOI:10.12360/CPB202307067
异硫氰酸苄酯通过激活p53和AMPK-FOXO1a信号通路诱导宫颈癌细胞周期阻滞和凋亡
Benzyl isothiocyanate induces cell cycle arrest and apoptosis in cervical cancer through activation of p53 and AMPK-FOXO1a signaling pathways
摘要
Abstract
Aim To investigate the effect of benzyl iso-thiocyanate(BITC)on the proliferation of mouse U14 cervical cancer cells and to explore the mechanism of cytotoxicity based on transcriptomic data analysis.Methods The effect of BITC on U14 cell activity was detected by MTT,nuclear morphological changes were observed by Hochest 33258 and fluorescent inverted microscope,cell cycle and apoptosis were determined by flow cytometry,and the transcriptome database of U14 cells before and after BITC(20 pmol·L-1)treatment was established based on Illumina Novaseq 6000 sequencing platform.The expression of key mole-cules in the signaling pathway was verified by qRT-PCR and Western blot.Results BITC inhibited the activity of U14 cells in a time-and concentration-de-pendent manner,blocked cells in Go/G1 phase,induced apoptosis,and up-regulated the expression of Bax,cytC,cleaved caspase-9/3,and down-regulated Bcl-2 and cleaved caspase-7;By transcriptome analysis,the differential genes were mainly enriched in cell cycle,FOXO,p53,apoptosis and other signaling pathways.qRT-PCR or Western blot verified that the expression of p53,p21,Ire1 a,Atf4,CHOP,AMPK,and FOXO1 a molecules were improved and Cyclin D3,Cyclin E,and Cdk2 molecules were reduced.Conclusions BITC blocks U14 cell cycle,induces apoptosis through caspase-3 mitochondria-dependent pathway and endo-plasmic reticulum stress pathway.The mechanism is closely related to p53 and AMPK-FOXO1a signaling pathway.关键词
异硫氰酸苄酯/宫颈癌/转录组/p53/FOXO/细胞周期/细胞凋亡Key words
benzyl isothiocyanate/cervical cancer/transcriptome/p53/FOXO/cell cycle/cell apoptosis分类
医药卫生引用本文复制引用
塔玛莎·库尔曼江,李金玉,王小静,李欣奕,王昊,解国轩,陈雲杰,温婷,程夕露,努尔阿米乃·麦麦提..异硫氰酸苄酯通过激活p53和AMPK-FOXO1a信号通路诱导宫颈癌细胞周期阻滞和凋亡[J].中国药理学通报,2024,40(1):114-125,12.基金项目
新疆维吾尔自治区重点研发计划项目子课题资助项目(No 2022B03018-5) （No 2022B03018-5）
新疆特殊环境物种多样性应用与调控重点实验室资助项目(XJTSWZ-2021-02) （XJTSWZ-2021-02）
新疆师范大学博士启动基金资助项目(No 3010010267). （No 3010010267）
