河北医学2024，Vol.30Issue(8)：1284-1290,7.DOI:10.3969/j.issn.1006-6233.2024.08.010
尿石素A调节AKT/mTOR信号通路对三阴性乳腺癌细胞恶性生物学行为的影响
Effect of Urolithin A on Malignant Biological Behavior of Triple-Negative Breast Cancer Cells via AKT/mTOR Signaling Pathway
摘要
Abstract
Objective:To investigate the effect of urolithin A(UA)on the malignant biological behavior of triple-negative breast cancer(TNBC)cells and its regulatory mechanism on the protein kinase B(AKT)/mammalian target of rapamycin(mTOR)signaling pathway.Methods:The safety and toxicity of UA were as-sessed on human normal breast epithelial cell line MCF-10A and TNBC cell line MDA-MB-231 using the CCK-8 assay.MDA-MB-231 cells were randomly divided into the following groups:MDA-MB-231,MDA-MB-231+UA,MDA-MB-231+AKT activator(SC79),and MDA-MB-231+UA+AKT activator(UA+SC79).The proliferation activity of each group was detected by colony formation assay.Cell migration and in-vasion abilities were examined by wound healing and Transwell assays.Apoptosis was assessed by flow cytome-try.The activation levels of AKT/mTOR signaling pathway-related proteins were detected by Western blot.Results:UA at a concentration of 7.5μmoL/L was determined to be safe for normal breast cells and toxic to breast cancer cells.Compared to the MDA-MB-231 group,the UA group showed decreased colony formation(105.67±9.18),cell migration rate(12.92±2.13),invasion cell count(56.33±3.68),and p-AKT/AKT(0.12±0.02)and p-mTOR/mTOR(0.16±0.03)levels(P＜0.05),while the apoptosis rate(22.1±1.75)increased(P＜0.05).In contrast,the SC79 group showed increased colony formation(222±17.57),cell mi-gration rate(62.7±6.14),invasion cell count(233.33±15.43),and p-AKT/AKT(0.58±0.07)and p-mTOR/mTOR(0.74±0.08)levels(P＜0.05),and decreased apoptosis rate(4.57±0.57)(P＜0.05).The addition of SC79 reversed the inhibitory effects of UA on the malignant biological behavior of MDA-MB-231 cells(P＜0.05).Conclusion:UA can inhibit the proliferation,migration,invasion,and anti-apoptotic activ-ities of TNBC cells by suppressing the AKT/mTOR signaling pathway.关键词
尿石素A/蛋白激酶B/雷帕霉素靶蛋白/三阴性乳腺癌Key words
Urolithin A/Protein kinase B/Mammalian target of rapamycin/Triple-negative breast cancer引用本文复制引用
阿吉古,韩记真,陈艳艳,赖巧蓉..尿石素A调节AKT/mTOR信号通路对三阴性乳腺癌细胞恶性生物学行为的影响[J].河北医学,2024,30(8):1284-1290,7.基金项目
新疆维吾尔自治区自然科学基金面上项目,(编号:2019D01C269) （编号:2019D01C269）
