转录组学和蛋白质组学分析天然雷博霉素类似物洛那霉素在乳腺癌细胞中的抗癌作用机制。
Transcriptomics and Proteomics Characterizing the Anticancer Mechanisms of Natural Rebeccamycin Analog Loonamycin in Breast Cancer Cells.
机构信息
Experimental Training Center of Basic Medical Science, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China.
Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Naval Medical University, Shanghai 200433, China.
出版信息
Molecules. 2022 Oct 17;27(20):6958. doi: 10.3390/molecules27206958.
The present study is to explore the anticancer effect of loonamycin (LM) in vitro and in vivo, and investigate the underlying mechanism with combined multi-omics. LM exhibited anticancer activity in human triple negative breast cancer cells by promoting cell apoptosis. LM administration inhibited the growth of MDA-MB-468 tumors in a murine xenograft model of breast cancer. Mechanistic studies suggested that LM could inhibit the topoisomerase I in a dose-dependent manner in vitro experiments. Combined with the transcriptomics and proteomic analysis, LM has a significant effect on O-glycan, p53-related signal pathway and EGFR/PI3K/AKT/mTOR signal pathway in enrichment of the KEGG pathway. The GSEA data also suggests that the TNBC cells treated with LM may be regulated by p53, O-glycan and EGFR/PI3K/AKT/mTOR signaling pathway. Taken together, our findings predicted that LM may target p53 and EGFR/PI3K/AKT/mTOR signaling pathway, inhibiting topoisomerase to exhibit its anticancer effect.
本研究旨在探讨洛那霉素（LM）在体外和体内的抗癌作用，并结合多组学研究探讨其潜在机制。LM 通过促进细胞凋亡在人三阴性乳腺癌细胞中表现出抗癌活性。LM 给药抑制了乳腺癌小鼠异种移植模型中 MDA-MB-468 肿瘤的生长。机制研究表明，LM 在体外实验中可呈剂量依赖性抑制拓扑异构酶 I。结合转录组学和蛋白质组学分析，LM 对富集的 KEGG 途径中的 O-聚糖、p53 相关信号通路和 EGFR/PI3K/AKT/mTOR 信号通路有显著影响。GSEA 数据还表明，用 LM 处理的 TNBC 细胞可能受 p53、O-聚糖和 EGFR/PI3K/AKT/mTOR 信号通路的调控。综上所述，我们的研究结果表明，LM 可能靶向 p53 和 EGFR/PI3K/AKT/mTOR 信号通路，抑制拓扑异构酶以发挥其抗癌作用。
Zotero 插件