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1.广州中医药大学 深圳医院(福田)治未病中心,广东 深圳;518034
2.广州中医药大学科技创新中心,广州 510405
3.深圳市 中医肿瘤医学中心,广东 深圳 518034
4.广州中医药大学深圳医院(福田)肿瘤科,广东 深圳 518034
5.圣约翰大学,美国 纽约 11439
主治医师,硕士。研究方向:中医药防治内科疾病。E-mail:511292381@qq.com
主治医师,硕士。研究方向:中西医结合防治肿瘤相关疾病。E-mail:llhyy2021@163.com
收稿日期:2025-03-17,
修回日期:2025-04-21,
录用日期:2025-05-28,
纸质出版日期:2025-07-30
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李鑫,方崇锴,黄越,等.参芪固本方调控IL-17信号通路改善癌因性疲乏的作用机制[J].中国药房,2025,36(14):1722-1729.
LI Xin,FANG Chongkai,HUANG Yue,et al.Mechanism of Shenqi guben formula in improving cancer-related fatigue by regulating IL-17 signaling pathway[J].ZHONGGUO YAOFANG,2025,36(14):1722-1729.
李鑫,方崇锴,黄越,等.参芪固本方调控IL-17信号通路改善癌因性疲乏的作用机制[J].中国药房,2025,36(14):1722-1729. DOI: 10.6039/j.issn.1001-0408.2025.14.06.
LI Xin,FANG Chongkai,HUANG Yue,et al.Mechanism of Shenqi guben formula in improving cancer-related fatigue by regulating IL-17 signaling pathway[J].ZHONGGUO YAOFANG,2025,36(14):1722-1729. DOI: 10.6039/j.issn.1001-0408.2025.14.06.
目的
2
基于网络药理学和细胞实验探讨参芪固本方改善癌因性疲乏(CRF)的作用机制。
方法
2
基于TCMSP等数据库挖掘参芪固本方活性成分及CRF相关靶点,并进行富集分析。采用白细胞介素17(IL-17)诱导A549细胞建立CRF细胞模型,使用低(1.0 mg/mL)、高质量浓度(1.5 mg/mL)参芪固本方干预,通过细胞划痕实验、流式细胞术、酶联免疫吸附测定、实时荧光定量聚合酶链式反应实验及Western blot等方法验证其对细胞活力、迁移、凋亡、炎症因子及其mRNA表达、凋亡相关蛋白和IL-17信号通路关键蛋白的影响。
结果
2
共得到84个活性成分及209个CRF交集靶点,其中槲皮素、山柰酚和木犀草素等为核心活性成分,肿瘤蛋白p53、丝氨酸/苏氨酸激酶1、IL-6、肿瘤坏死因子(TNF)等为核心靶点,IL-17、TNF、磷脂酰肌醇3激酶/蛋白激酶B信号通路为关键通路。与IL-17干预组比较,IL-17+参芪固本方低、高质量浓度组细胞的迁移率,B淋巴细胞瘤2(Bcl-2)蛋白表达,上清液中IL-6、TNF-α水平,IL-17受体A(IL-17RA)、IL-6、TNF-α mRNA表达,IL-17RA、核因子κB p65亚基(p65)蛋白表达和磷酸化p65 (p-p65)/p65比值均显著降低或下调(
P
<0.05);凋亡率,Bcl-2相关X蛋白(Bax)、切割型胱天蛋白酶3蛋白表达、Bax/Bcl-2比值,磷酸化p38丝裂原活化的蛋白激酶(p-p38 MAPK)蛋白表达、p-p38 MAPK/p38 MAPK比值均显著升高或上调(
P
<0.05);且高质量浓度组上述指标的改善大多优于低质量浓度组(
P
<0.05)。
结论
2
参芪固本方可能通过调控IL-17信号通路、抑制炎症因子表达、激活p38 MAPK依赖的凋亡过程来改善CRF。
OBJECTIVE
2
To explore the mechanism of Shenqi guben formula (SQGB) in improving cancer-related fatigue (CRF) based on network pharmacology and cellular experiments.
METHODS
2
Active components of SQGB and CRF-related targets were identified on the basis of databases such as the Traditional Chinese Medicine Systems Pharmacology platform. An
in vitro
CRF cell model was established by inducing A549 cells with interleukin-17 (IL-17). Cells were treated with low (1.0 mg/mL) or high (1.5 mg/mL) concentrations of SQGB. The effects on cell viability, migration, apoptosis, inflammatory factors, mRNA expression, apoptosis-related proteins and key proteins of IL-17 signaling pathway were evaluated using scratch assay, flow cytometry, ELISA, real-time fluorescent quantitative PCR and Western blot analysis.
RESULTS
2
SQGB contained 84 active components acting on 209 potential CRF targets. Among these, quercetin, kaempferol, and luteolin were identified as the core components of the compound. Core targets included tumor protein p53, AKT serine/threonine kinase 1, IL-6, and tumor necrosis factor (TNF). IL-17, TNF and phosphatidylinositol-3-kinase-serine/threonine protein kinase (PI3K/Akt) signaling pathways were identified as crucial pathways. Compared with IL-1
7 intervention group, the cell migration rate, B-cell lymphoma 2 (Bcl-2) protein expression, the levels of IL-6 and TNF-α in the supernatant, mRNA expression of IL-17 receptor A (IL-17RA), TNF-α, and IL-6, as well as the protein expression of IL-17RA and nuclear factor kappa-B p65 subunit (p65), and phosphorylated (p)-p65/p65 ratio in IL-17+SQGB low- and high- quality concentration groups were all significantly decreased or down-regulation (
P
<0.05); the apoptosis rate, expression levels of Bcl-2 associated X protein (Bax) and cleaved caspase-3 protein, the ratio of Bax/Bcl-2, the expression level of p-p38 protein, and the p-p38/p38 ratio were all significantly increased or up-regulated (
P
<0.05). Moreover, the improvement effects of these indicators were mostly better in the high-quality concentration groups compared to the low-quality concentration groups (
P
<0.05).
CONCLUSIONS
2
SQGB ameliorates CRF by regulating the IL-17 signaling pathway, inhibiting the expression of inflammatory factors, and activating p38 MAPK-dependent apoptosis pathway.
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