摘要
目的阐明青蒿琥酯(artesunate,ART)在乳腺癌发展过程中所发挥的功能及可能的作用机制。方法设置用不同浓度ART处理MCF-7、MDA-MB-231为实验组,0μmol·L^(-1)ART处理细胞为对照组。通过MTT、平板单克隆实验测定ART对乳腺癌细胞生长能力的影响;Transwell实验探究ART对乳腺癌细胞侵袭以及迁移能力的影响;采用流式细胞术检测ART对乳腺癌细胞周期及其凋亡的影响;通过转录组测序分析及RT-qPCR实验方法检测并验证ART在乳腺癌细胞中可能的作用机制。结果经ART处理后的两种乳腺癌细胞MCF-7、MDA-MB-231其增殖、迁移以及侵袭能力与对照组相比均明显下降,ART作用后的乳腺癌细胞其G 0-G 1期细胞比例明显增加,并且乳腺癌细胞凋亡率明显上升。转录组测序结果提示,ART可能通过下调S期激酶相关蛋白2(S-phase kinase associated protein 2,Skp2)基因的表达、上调周期蛋白抑制因子1A(cyclin dependent kinase inhibitor 1A,CDKN1A)基因的表达调控乳腺癌细胞的周期以达到抑制乳腺癌细胞发生发展的目的。结论ART可通过影响Skp2基因、CDKN1A基因的表达抑制乳腺癌细胞的发展。
Aim To explore the effect of artesunate(ART)on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action.Methods MCF-7(30μmol·L^(-1))and MDA-MB-231(60μmol·L^(-1))cultured in complete medium containing artesunate were set as the experimental group,and cells cultured in complete medium with ART(0μmol·L^(-1))were used as the blank control group.The effect of ART on the growth ability of breast cancer cells was determined by MTT and plate monoclonal assay,and the influence of ART on the invasion as well as migration ability of breast cancer cells was investigated by Transwell assay.The effect of ART on breast cancer cell cycle and its apoptosis were detected by flow cytometry.The possible mechanism of action of ART on breast cancer cells was analyzed by transcriptome sequencing.Results The proliferation,migration and invasion ability of MCF-7 and MDA-MB-231 cells were significantly reduced after ART treatment compared with the control group,and the cell cycle of breast cancer cells was arrested at G 0-G 1 phase after ART treatment,and promoted apoptosis in breast cancer cells.Compared with the control group,transcriptome sequencing suggested that ART might regulate the cycle of breast cancer cells by down-regulating the expression of Skp2 gene and up-regulating the expression of CDKN1A gene,ultimately inhibiting the development of breast cancer.Conclusions The Chinese patent medicine artesunate can inhibit the development of breast cancer cells by affecting the expression of Skp2 gene and CDKN1A gene.Via investigation of the role of ART in breast cancer,this research provides a research direction as well as a theoretical basis for the development of novel highly effective,low-toxicity and low-cost drugs for breast cancer treatment.
作者
孙丽婷
沈冠彤
胡晓玲
朱飞
秦楠
连科
康静
岳竞
师如意
SUN Li-ting;SHEN Guan-tong;HU Xiao-ling;ZHU Fei;QIN Nan;LIAN Ke;KANG Jing;YUE Jing;SHI Ru-yi(Dept of Medical Cell Biology and Genetics,Shanxi Medical University,Taiyuan 030001,China;Dept of Pharmacology,Shanxi Medical University,Taiyuan 030001,China;College of Pharmaceutical and Food Engineering,Shanxi University of Chinese Medicine,Jinzhong Shanxi 030619,China;Shanxi Bethune Hospital,Shanxi Academy of Medical Sciences,Tongji Shanxi Hospital,Third Hospital of Shanxi Medical University,Taiyuan 030032,China)
出处
《中国药理学通报》
CAS
CSCD
北大核心
2023年第9期1675-1681,共7页
Chinese Pharmacological Bulletin
基金
山西省基础研究计划自然科学研究面上项目(No 20210302123293)
细胞生理学教育部重点实验室(山西医科大学)2022年度开放基金面上项目(No CPOF202212)
2023年度山西省中医药科研课题(No 2023ZYYC2027)。
关键词
乳腺癌
青蒿琥酯
细胞增殖
细胞迁移
细胞侵袭
细胞周期
细胞凋亡
breast cancer
artesunate
cell proliferation
cell migration
cell invasion
cell cycle
cell apoptosis
