姜黄素通过调控PI3K-Akt信号途径抑制三阴性乳腺癌Hs578T细胞的增殖  

Curcumin Suppresses Proliferation in TNBC Hs578T Cells by Modulating the PI3K-Akt Signaling Pathway

作　　者：陈泽 李梦晗[2] 李雪灵 张青 卢品君 何涛 甘淋 CHEN Ze;LI Menghan;LI Xueling;ZHANG Qing;LU Pinjun;HE Tao;GAN Lin(Institute of Medical Cancer,School of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,China;Department of Cardiovascular Medicine,The First Affiliated Hospital of Kunming Medical University,Kunming 650000,China;Department of Pediatrics,Southwest Medical University,Luzhou 646000,China;Department of Dermatology,The Affiliated Hospital,Southwest Medical University,Luzhou 646000,China;Department of Nursing,The Affiliated Hospital,Southwest Medical University,Luzhou 646000,China;Department of Biochemistry and Molecular Biology,School of Basic Medical Sciences,Southwest Medical University,Luzhou 646000,China)

机构地区：[1]西南医科大学基础医学院肿瘤医学研究所,泸州646000 [2]昆明医科大学第一附属医院心血管内科,昆明650000 [3]西南医科大学儿科学系,泸州646000 [4]西南医科大学附属医院皮肤科,泸州646000 [5]西南医科大学附属医院护理部,泸州646000 [6]西南医科大学基础医学院生物化学与分子生物学教研室,泸州646000

出　　处：《西南医科大学学报》2025年第2期184-191,共8页Journal of Southwest Medical University

基　　金：四川省科技厅科技计划联合创新专项(2022YFS0623);省级大学生创新创业计划项目(S202310632313)。

摘　　要：目的本研究旨在运用RNA测序和生物信息学等预测姜黄素对三阴性乳腺癌(triple negative breast cancer,TNBC)Hs578T细胞的抗癌机制,并通过体外实验对潜在的分子机制进行验证。方法用姜黄素处理Hs578T细胞后,采用CCK-8法检测姜黄素对细胞增殖能力的影响,使用流式细胞术检测姜黄素对细胞凋亡和周期的影响,再使用Transwell实验检测姜黄素对细胞运动能力的影响。然后进行转录组测序、构建PPI网络和富集分析对姜黄素的抗癌机制进行预测,最后使用蛋白免疫印迹技术检测姜黄素对Hs578T细胞增殖相关蛋白的影响。结果姜黄素作用于Hs578T细胞24 h后,CCK8检测结果提示姜黄素的IC50约为20μmol/L。使用20μmol/L姜黄素刺激的Hs578T细胞为实验组,未进行姜黄素刺激的细胞为对照组。较对照组,实验组结果显示姜黄素能显著抑制Hs578T细胞的增殖能力,具有时间和浓度依赖性;显著诱导细胞凋亡,阻滞细胞周期于G2/M期;显著抑制细胞的迁移和侵袭能力,相较于对照组差异均具有统计学意义(P<0.05)。PPI网络分析的结果显示差异表达基因表达的蛋白质之间具有相互作用关系。转录组测序和生物信息学分析的结果显示,姜黄素通过参与多条信号通路发挥抗癌作用,如癌症中的信号通路、PI3K-Akt信号通路等。蛋白印迹结果显示姜黄素能在Hs578T细胞中显著抑制m TOR、p-Akt、Akt、p-S6、S6蛋白表达。结论姜黄素可能通过抑制PI3K-Akt信号通路相关蛋白的表达来发挥其抗增殖作用,为临床姜黄素治疗TNBC提供了理论依据和实验基础。Objective This study aims to employ RNA sequencing and bioinformatics to predict the anticancer mechanisms of curcumin in triple-negative breast cancer Hs578T cells and to validate these potential molecular mechanisms through in vitro experi⁃ments.Methods After treating Hs578T cells with curcumin,their proliferative capacity was evaluated using the cell counting kit-8(CCK-8)assay.The impact of curcumin on apoptosis and cell cycle progression was assessed in these cells via flow cytometry.The Transwell assay was employed to examine curcumin's effects on cell motility.Then transcriptome sequencing,construction of PPI net⁃work and enrichment analysis were performed to predict the anti-cancer mechanism of curcumin.Finally,western blot analysis was used to determine curcumin's influence on the expression of proteins associated with the proliferation of Hs578T cells.Results After 24 hours of treatment with curcumin,the CCK-8 assay determined that the IC50 value for curcumin in human Hs578T cells was approximately 20μmol/L.Cells exposed to 20μmol/L of curcumin formed the experimental group,while untreated cells served as the control group.Compared to the control group,curcumin treatment significantly reduced the proliferative capacity of Hs578T cells in a time-and concentration-dependent manner;it significantly induced apoptosis and blocked the cell cycle in the G2/M phase;and it significantly decreased migration and invasion capabilities,all of which were statistically significant(P<0.05).The results of the PPI net⁃work showed interactive relationships between proteins expressed by differentially expressed genes.The results of transcriptome sequencing and bioinformatics analysis showed that curcumin exerted anticancer effects by participating in several signaling pathways,such as the pathways in cancer and the PI3K-Akt signaling pathway.Western blot analysis further revealed that curcumin substantially lowered the expression levels of key proteins involved in cell structure,growth,and proliferation,specifically

关 键 词：姜黄素 三阴性乳腺癌 生物信息学 PI3K-AKT 

分 类 号：R737.9[医药卫生—肿瘤]