Hao Pengfei, Zhang Chaoyun, Bian Hua, Li Yixian
Nanyang Institute of Technology, Henan Key Laboratory of Zhang Zhongjing Formulae and Herbs for Immunoregulation, Nanyang, 473000, China.
NMPA Key Laboratory for Quality Control of Traditional Chinese Medicine (Chinese Materia Medica and Prepared Slices), Zhengzhou, 450000, China.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun;397(6):4089-4104. doi: 10.1007/s00210-023-02859-x. Epub 2023 Nov 28.
Myricetin is a natural flavonoid with anti-cancer and anti-inflammatory effects, but its mechanism for treating lung adenocarcinoma (LUAD) remains unclearly. Therefore, bioinformatics, in silico and in vitro experiments were employed to elucidate this issue in this study. The core targets of myricetin against LUAD were screened by PharmaMapper (v2017), Assistant for Clinical Bioinformatics, STRING (v11.5) and Cytoscape (v3.8.1). Using Kaplan-Meier Plotter (v2022.04.20), UALCAN (v2021.12.13) and GEPIA (v2.0) databases, the correlation between core genes and the prognosis of LUAD patients were analyzed, and the expression levels of core genes were verified. In silico studies were used to analyze the binding energies and sites of myricetin with core genes. The effects of myricetin on H1975 cells were explored through thiazolyl blue (MTT), cell migration, colony formation and western blot assays. A total of 72 potential targets of myricetin against LUAD were identified through bioinformatics. Among the four core targets obtained by multiple networks and in silico assays, the up-regulated MMP9 (HR = 1.14 (1-1.29), logrank P = 0.046) and down-regulated PIK3R1 (HR = 0.58 (0.51-0.66), logrank P < 1E-16) were positively correlated with poor survival outcomes in LUAD patients. In vitro experiments demonstrated that myricetin inhibited the proliferation and migration of H1975 cells, promoting their apoptosis. Myricetin inhibits the proliferation of H1975 cells and induces cell apoptosis through its influence on the expression levels of MMP1, MMP3, MMP9, and PIK3R1 and regulating the multiple pathways these genes participate in. Both MMP9 and PIK3R1 are potential biomarkers for LUAD.
杨梅素是一种具有抗癌和抗炎作用的天然黄酮类化合物，但其治疗肺腺癌（LUAD）的机制仍不清楚。因此，本研究采用生物信息学、计算机模拟和体外实验来阐明这一问题。通过PharmaMapper（v2017）、临床生物信息学助手、STRING（v11.5）和Cytoscape（v3.8.1）筛选出杨梅素抗LUAD的核心靶点。利用Kaplan-Meier Plotter（v2022.04.20）、UALCAN（v2021.12.13）和GEPIA（v2.0）数据库，分析核心基因与LUAD患者预后的相关性，并验证核心基因的表达水平。通过计算机模拟研究分析杨梅素与核心基因的结合能和结合位点。通过噻唑蓝（MTT）、细胞迁移、集落形成和蛋白质免疫印迹分析，探讨杨梅素对H1975细胞的影响。通过生物信息学共鉴定出72个杨梅素抗LUAD的潜在靶点。在通过多个网络和计算机模拟分析获得的四个核心靶点中，上调的基质金属蛋白酶9（MMP9）（风险比[HR]=1.14（1 - 1.29），对数秩检验P=0.046）和下调的磷脂酰肌醇-3激酶调节亚基1（PIK3R1）（HR=0.58（0.51 - 0.66），对数秩检验P<1E - 16）与LUAD患者较差的生存结果呈正相关。体外实验表明，杨梅素抑制H1975细胞的增殖和迁移，促进其凋亡。杨梅素通过影响基质金属蛋白酶1（MMP1）、基质金属蛋白酶3（MMP3）、MMP9和PIK3R1的表达水平并调节这些基因参与的多条途径，抑制H1975细胞的增殖并诱导细胞凋亡。MMP9和PIK3R1均为LUAD的潜在生物标志物。
