毛蕊异黄酮通过 PI3K-AKT 和 EGFR-RAS-RAF 通路发挥抗乳腺癌作用。
Syringin exerts anti-breast cancer effects through PI3K-AKT and EGFR-RAS-RAF pathways.
机构信息
Faculty of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China.
Key Laboratory of Traditional Chinese Medicine Resources and Chemistry of Hubei Province, Wuhan, 430061, China.
出版信息
J Transl Med. 2022 Jul 6;20(1):310. doi: 10.1186/s12967-022-03504-6.
BACKGROUND
Breast cancer (BC) is one of the most common malignant tumors with the highest mortality in the world. Modern pharmacological studies have shown that Syringin has an inhibitory effect on many tumors, but its anti-BC efficacy and mechanism are still unclear.
METHODS
First, Syringin was isolated from Acanthopanax senticosus (Rupr. & Maxim.) Harms (ASH) by systematic solvent extraction and silica gel chromatography column. The plant name is composed of genus epithet, species additive words and the persons' name who give its name. Then, the hub targets of Syringin against BC were revealed by bioinformatics. To provide a more experimental basis for later research, the hub genes which could be candidate biomarkers of BC and a ceRNA network related to them were obtained. And the potential mechanism of Syringin against BC was proved in vitro experiments.
RESULTS
Syringin was obtained by liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR), and high-performance liquid chromatography (HPLC). Bioinformatics results showed that MAP2K1, PIK3CA, HRAS, EGFR, Caspase3, and PTGS2 were the hub targets of Syringin against BC. And PIK3CA and HRAS were related to the survival and prognosis of BC patients, the PIK3CA-hsa-mir-139-5p-LINC01278 and PIK3CA-hsa-mir-375 pathways might be closely related to the mechanism of Syringin against BC. In vitro experiments confirmed that Syringin inhibited the proliferation and migration and promoted apoptosis of BC cells through the above hub targets.
CONCLUSIONS
Syringin against BC via PI3K-AKT-PTGS2 and EGFR-RAS-RAF-MEK-ERK pathways, and PIK3CA and HRAS are hub genes for adjuvant treatment of BC.
背景
乳腺癌（BC）是全球最常见的恶性肿瘤之一，死亡率最高。现代药理学研究表明，紫丁香苷对多种肿瘤具有抑制作用，但对其抗 BC 疗效及机制尚不清楚。
方法
首先，采用系统溶剂萃取和硅胶柱层析法从刺五加（ASH）中分离出紫丁香苷。然后，通过生物信息学揭示了紫丁香苷抗 BC 的枢纽靶标。为了为以后的研究提供更充分的实验依据，获得了可能成为 BC 候选生物标志物的枢纽基因和与之相关的 ceRNA 网络。并通过体外实验验证了紫丁香苷抗 BC 的潜在机制。
结果
通过液相色谱-质谱联用（LC-MS）、核磁共振（NMR）和高效液相色谱（HPLC）得到紫丁香苷。生物信息学结果表明，MAP2K1、PIK3CA、HRAS、EGFR、Caspase3 和 PTGS2 是紫丁香苷抗 BC 的枢纽靶标。并且 PIK3CA 和 HRAS 与 BC 患者的生存和预后有关，PIK3CA-hsa-mir-139-5p-LINC01278 和 PIK3CA-hsa-mir-375 通路可能与紫丁香苷抗 BC 的机制密切相关。体外实验证实，紫丁香苷通过上述枢纽靶点抑制 BC 细胞的增殖、迁移和促进凋亡。
结论
紫丁香苷通过 PI3K-AKT-PTGS2 和 EGFR-RAS-RAF-MEK-ERK 通路以及 PIK3CA 和 HRAS 发挥抗 BC 作用，PIK3CA 和 HRAS 是 BC 辅助治疗的枢纽基因。
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