甘草酸对人肺腺癌细胞的作用及其机制研究

doi:10.3969/j.issn.1004-616x.2025.01.010

摘要/Abstract

摘要： 目的：探究甘草酸对体外培养的人肺腺癌细胞的作用及其作用机制。方法： MTT法检测0.5~6 mmol/L的甘草酸作用人肺腺癌A549细胞、NCI-H1299细胞及人正常肺上皮Beas-2b细胞、人脐静脉内皮HUVECs细胞48 h后对其生长活力的影响；流式细胞术测定4 mmol/L甘草酸处理48 h对A549细胞周期及凋亡的影响；网络药理学方法预测甘草酸抗肺腺癌关键靶点及其通路；逆转录实时荧光定量PCR(RT-qPCR)及Western blot法验证甘草酸作用于A549细胞的关键靶点。结果： 1~6 mmol/L甘草酸作用48 h可显著抑制人肺腺癌A549和NCI-H1299细胞的活力，但对人肺正常上皮Beas-2b细胞及人脐静脉内皮HUVECs细胞的抑制作用较弱。4 mmol/L甘草酸作用A549细胞48 h后，对照组凋亡细胞比例为(3.73±1.43)%，甘草酸作用组的凋亡细胞比例为(44.41±10.28)%；对照组G₀/G₁期细胞比例为(45.7±0.98)%，甘草酸作用组比例为(53.03±2.25)%。网络药理学预测甘草酸抗肺腺癌关键靶点有caspase 3、STAT3、SRC、MMP9及PTGS2，涉及细胞凋亡、周期阻滞、氧化应激等信号通路；实验发现，甘草酸可显著降低A549细胞SRC mRNA和PTGS2 mRNA表达，抑制p-STAT3的表达，激活caspase 3的裂解活化。结论：体外研究发现，一定浓度的甘草酸可杀伤人肺腺癌细胞A549，主要机制是诱导人肺腺癌细胞周期阻滞和凋亡，可能涉及SRC、PTGS2、p-STAT3的表达水平下调及caspase 3激活。

关键词: 甘草酸, 肺腺癌, 细胞凋亡, 细胞周期阻滞, 关键靶点, 胱天蛋白酶3

Abstract: OBJECTIVE： To explore whether glycyrrhizic acid has an anti-lung adenocarcinoma effect and its mechanism in vitro. METHODS： Human lung adenocarcinoma cells A549，NCI-H1299，normal human lung epithelial cells Beas-2b，and human umbilical vein endothelial cells (HUVECs) were treated with glycyrrhizic acid at concentrations of 0.5-6 mmol/L for 48 hours. The MTT assay was used to detect effects on growth and viability. Flow cytometry was used to assess effects on cell cycle and apoptosis in A549 cells，comparing the untreated with cells treated with 4 mmol/L glycyrrhizic acid. Network pharmacology was employed to predict key targets and pathways impacted by glycyrrhizic acid. Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blotting were used to verify key targets after treatment with 4 mmol/L glycyrrhizic acid in A549 cells. RESULTS： At concentrations of 1-6 mmol/L，glycyrrhizic acid significantly inhibited the viability of A549 and NCI-H1299 cells，while showing a weaker inhibitory effect on normal lung epithelial cells Beas-2b and HUVECs. After treatment with 4 mmol/L glycyrrhizic acid，the proportion of apoptotic cells in the control group was (3.73±1.43)%，compared to (44.41±10.28)% in the treatment group. The proportion of cells in the G₀/G₁ phase in the control group was (45.7±0.98)%，while the treatment group had (53.03±2.25)%. Network pharmacology predicted the key targets were caspase 3，STAT3，SRC，MMP9，and PTGS2，which are involved in apoptosis，cell cycle arrest，and oxidative stress signaling pathways. In addition，glycyrrhizic acid significantly reduced the mRNA expression of SRC and PTGS2 in A549 cells，inhibited the expression of p-STAT3，and activated the cleavage of caspase 3. CONCLUSION： Our in vitro studies indicate that glycyrrhizic acid selectively killed human lung adenocarcinoma cells A549，primarily through the induction of cell cycle arrest and apoptosis，possibly involving downregulation of SRC，PTGS2，and p-STAT3 expression levels and activation of caspase 3.

Key words: glycyrrhizic acid, lung adenocarcinoma, cell apoptosis, cell cycle arrest, key targets, caspase 3

中图分类号:

R961

黄吉, 李子烜, 徐嘉琪, 罗绣, 孙震晓. 甘草酸对人肺腺癌细胞的作用及其机制研究[J]. 癌变·畸变·突变, 2025, 37(1): 56-62.

HUANG Ji, LI Zixuan, XU Jiaqi, LUO Xiu, SUN Zhenxiao. Effect of glycyrrhizic acid on human lung adenocarcinoma cells and its mechanism[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2025, 37(1): 56-62.

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