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赤芍抗肺癌靶点及生物学分子机制:网络药理学分析与实验验证

Anti-Lung Cancer Targets of Radix Paeoniae Rubra and Biological Molecular Mechanism: Network Pharmacological Analyses and Experimental Validation.

作者信息

Ma Yunfei, Li Guangda, Yu Mingwei, Cao Kexin, Li Qiwei, Sun Xu, Yang Guowang, Wang Xiaomin

机构信息

Department of Oncology, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People's Republic of China.

School of Graduates, Beijing University of Chinese Medicine, Beijing, People's Republic of China.

出版信息

Onco Targets Ther. 2021 Mar 16;14:1925-1936. doi: 10.2147/OTT.S261071. eCollection 2021.

Abstract

OBJECTIVE

To systematically explore the pharmacological mechanism of Radix Paeoniae Rubra (RPR) against lung cancer (LC).

METHODS

A network pharmacology approach, which involves active ingredients and target forecast, network construction, gene ontology and pathway enrichment, was employed in this research. In addition, the effect of Baicalein (BAI) in RPR on A549 cells was researched in vitro and in vivo.

RESULTS

A total of 159 targets of the 29 active components in RPR were procured by pharmacokinetic parameters. The network analysis showed that β-sitosterol, baicalein, (+)-catechin, ellagic acid, stigmasterol, (2R, 3R)-4-methoxyl-distylin were the main ingredients and JUN, VEGFA, BCL2 were the hub targets of RPR in the treatment of LC. The functional enrichment analysis showed that RPR likely was useful to LC by regulating numerous pathways including Pathways in cancer, MAPK signaling pathway and so on. MTT results showed that 100μM, 200μM, 400μM of BAI had a time and dose-dependent inhibitory effect on A549 cells proliferation; Wound healing and transwell assays showed that 100μM, 200μM, 400μM of BAI could significantly restrain the migration and invasion of A549 cells; Flow cytometry assay results showed that 100μM, 200μM, 400μM of BAI could induce apoptosis of A549 cells. In vivo, BAI (50, 100 mg/kg) significantly inhibited tumor growth and promoted apoptosis of tumor cells compared with the control group.

CONCLUSION

BAI in RPR may exert anti-tumor effects by inhibiting the proliferation, migration and invasion of LC cells, and inducing the apoptosis of LC cells.

摘要

目的

系统探究赤芍抗肺癌的药理机制。

方法

本研究采用网络药理学方法,包括活性成分及靶点预测、网络构建、基因本体和通路富集。此外,体外和体内研究了赤芍中的黄芩苷对A549细胞的作用。

结果

通过药代动力学参数获得了赤芍中29种活性成分的159个靶点。网络分析表明,β-谷甾醇、黄芩苷、(+)-儿茶素、鞣花酸、豆甾醇、(2R,3R)-4-甲氧基二氢茋是主要成分,JUN、VEGFA、BCL2是赤芍治疗肺癌的核心靶点。功能富集分析表明,赤芍可能通过调节包括癌症通路、MAPK信号通路等众多通路对肺癌发挥作用。MTT结果显示,100μM、200μM、400μM的黄芩苷对A549细胞增殖具有时间和剂量依赖性抑制作用;划痕实验和Transwell实验表明,100μM、200μM、400μM的黄芩苷可显著抑制A549细胞的迁移和侵袭;流式细胞术检测结果表明,100μM、200μM、400μM的黄芩苷可诱导A549细胞凋亡。在体内,与对照组相比,黄芩苷(50、100mg/kg)显著抑制肿瘤生长并促进肿瘤细胞凋亡。

结论

赤芍中的黄芩苷可能通过抑制肺癌细胞的增殖、迁移和侵袭以及诱导肺癌细胞凋亡发挥抗肿瘤作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a3a3/7981145/5a0d1ce13855/OTT-14-1925-g0001.jpg

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