食品工业科技2025，Vol.46Issue(7)：355-364,10.DOI:10.13386/j.issn1002-0306.2024050320
基于mTOR/HIF-1α/VEGF信号通路探讨菟丝子醇提物对4T1乳腺癌细胞增殖的抑制作用
Inhibition of Proliferation of 4T1 Breast Cancer Cells by Cuscuta Alcohol Extract Based on mTOR/HIF-1α/VEGF Signaling Pathway
摘要
Abstract
Objective:To examine the inhibitory effects and mechanisms of Cuscuta alcohol extract on the proliferation of 4T1 breast cancer cells,both in vitro and in vivo.Methods:MTT,scratch,transwell,and flow cytometric assays were used to examine the effects of Cuscuta alcohol extract on the proliferation,migration,invasion,and apoptosis of 4T1 breast cancer cells in vitro.Additionally,an in vivo 4T1 tumor-bearing mouse model was established.ELISA kits measured TNF-α,IL-2,and IL-10 levels in 4T1 tumor-bearing mice after 14 days of intragastric Cuscuta alcohol extract administration.Concurrently,tumor tissues from both the model mice and the high-dose Cuscuta alcohol extract group were analyzed using transcriptome sequencing to identify differentially expressed genes.GO and KEGG enrichment analyses were conducted,and the Western Blot assays were performed to verify the expression of the mTOR/HIF-1α/VEGF signaling pathway.Results:Cuscuta alcohol extract(400,800 and 1200 μg/mL)significantly reduced the proliferation,migration,and invasion of 4T1 breast cancer cells(P＜0.05,P＜0.01),and enhanced their apoptosis(P＜0.01),compared to blank control.In the in vivo model,Cuscuta alcohol extract(6.24 and 12.48 g/kg)significantly increased the serum levels of TNF-α,IL-2,and IL-10 in mice relative to model group(P＜0.05,P＜0.0l).Transcriptome sequencing identified 512 differentially expressed genes,including 154 upregulated and 358 downregulated genes.GO enrichment analysis identified 1870 items,while KEGG enrichment analysis enriched for cytokine receptor interactions,HIF-1 signalling pathway,IL-17 signalling pathway and other signalling pathways.The extract reduced the p-mTOR,HIF-1α,p-RPS6K,p-P70S6K,VEGF,and VEGFR2 protein expression levels in tumor tissues in a dose-dependent manner(P＜0.05,P＜0.01).Conclusions:The alcohol extract of Cuscuta inhibits the proliferation of 4T1 breast cancer cells and increase the serum expression levels of inflammatory factors in mice.Its antitumor mechanism is related to the modulation of the mTOR/HIF-1 α/VEGF signaling pathway.关键词
菟丝子/乳腺癌/转录组/mTOR/HIF-1α/VEGF信号通路Key words
Cuscuta/breast cancer/transcriptomics/mTOR/HIF-1 α/VEGF signaling pathway分类
医药卫生引用本文复制引用
宋辉,黄晓俏,孙向明,胡扬,单文猜,汤静,李文兰..基于mTOR/HIF-1α/VEGF信号通路探讨菟丝子醇提物对4T1乳腺癌细胞增殖的抑制作用[J].食品工业科技,2025,46(7):355-364,10.基金项目
黑龙江省重点研发计划(2022ZX02C08) （2022ZX02C08）
黑龙江省"双一流"学科协同创新成果建设项目(LJGXCG2024-P33) （LJGXCG2024-P33）
黑龙江省博士后项目(LBH-Z20023) （LBH-Z20023）
2022年哈尔滨商业大学博士科研启动支持计划(22BQ15). （22BQ15）
