研究动态
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通过网络药理学和实验验证阐明茅术抗结直肠癌机制。

Elucidation of the anti-colorectal cancer mechanism of Atractylodes lancea by network pharmacology and experimental verification.

发表日期:2024 Aug 22
作者: Guangliang Wang, Chuangchuang Guo, Hui Pi, Yu Wang, Shuyun Lin, Keyi Bi, Ming Zhang, Na Wang, Guojun Zhao
来源: GENES & DEVELOPMENT

摘要:

《神农本草》中记载的茅术可用于治疗胃肠道疾病。然而,其在结直肠癌(CRC)治疗中的作用、核心和活性成分以及机制仍不清楚。因此,通过网络药理学和实验验证来阐明茅术的功效、核心活性成分和分子机制。我们发现茅苍术有28个有效活性成分和213个潜在靶点。证实了苍术与CRC之间相互作用的73个基因。富集分析显示2033个GO生物过程项目和144个KEGG通路。生存和分子对接分析表明,木犀草素作为核心成分与这些基因(基质金属蛋白酶 3 (MMP3)、基质金属蛋白酶 9 (MMP9)、金属蛋白酶组织抑制剂 1 (TIMP1)、血管内皮生长因子 A (VEGFA))相互作用,最低的结合能,这些基因参与构建 CRC 的预后模型。细胞表型实验表明,木犀草素可能通过磷酸肌醇3激酶/丝氨酸/苏氨酸激酶Akt(PI3K/AKT)途径抑制CRC细胞的增殖和迁移,下调MMP3、MMP9、TIMP1、VEGFA的表达。综上所述,苍术可能通过其核心活性成分木犀草素抑制CRC细胞的增殖和迁移,从而抑制MMP3、MMP9、TIMP1、VEGFA的表达,可能是通过PI3K/AKT通路。
Atractylodes lancea which was listed in "Shennong's Materia Medica" and could be used to treat gastrointestinal-associated diseases. However, its roles, core and active ingredients, and mechanisms in treatment of colorectal cancer (CRC) were still unknown. Therefore, network pharmacology and experimental validation were used to clarify the effects, core active ingredients and molecular mechanisms of Atractylodes lancea. We found that Atractylodes lancea has 28 effective active components and 213 potential targets. Seventy-three genes which demonstrate interaction between the Atractylodes lancea and CRC were confirmed. Enrichment analysis showed that 2033 GO biological process items and 144 KEGG pathways. Survival and molecular docking analysis revealed that luteolin as the core component interacted with these genes (Matrix metalloproteinase 3 (MMP3), Matrix metalloproteinase 9 (MMP9), Tissue inhibitor of metalloproteinases 1 (TIMP1), Vascular endothelial growth factor A (VEGFA)) with the lowest binding energy, and these genes were involved in building a prognostic model for CRC. Cellular phenotyping experiments showed that luteolin could inhibit the proliferation and migration of CRC cells and downregulate the expression of MMP3, MMP9, TIMP1, VEGFA probably by Phosphoinositide 3-kinase/ serine/threonine kinase Akt (PI3K/AKT) pathway. To conclude, Atractylodes lancea could inhibit proliferation and migration of CRC cells through its core active ingredient (luteolin) to suppress the expression of MMP3, MMP9, TIMP1, VEGFA probably by PI3K/AKT pathway.