Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis.

Molecular targets of Yangyin Fuzheng Jiedu Prescription in the treatment of hepatocellular carcinoma based on network pharmacology analysis.
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基于网络药理学分析养阴扶正解毒方治疗肝癌的分子靶点

DOI:
10.1186/s12935-020-01596-y
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发表时间:
2020-11-09
影响因子:
5.8
通讯作者:
Yang Z
Yang Z
中科院分区:
医学2区
文献类型:
--
作者:
Yan F;Feng M;Wang X;Wang P;Xie Y;Liu X;Li W;Yang Z

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养阴扶正解毒方是治疗原发性肝癌的传统中药。其潜在的靶点和分子机制尚不清楚。因此,本研究拟通过网络药理学分析和体外验证,探讨YFJP的分子作用机制。通过单因素和多因素分析及生存分析,发现饮酒、AFP ≥ 400 ng/l、基线门静脉癌栓、总胆红素≥ 18.8 μM是肝癌患者预后不良的独立危险因素,而红细胞计数≥ 4 × 109/l和中医治疗是独立保护因素。此外,YFJP延长了HCC患者的累积生存期。利用在线药理学方法,共获得58个相关化合物和53个分子靶点。通过划痕实验、Transwell实验、EdU实验、TUNEL染色等方法,我们发现YFJP含药血清在体外抑制肝癌细胞的迁移、侵袭和增殖,并诱导细胞凋亡。YFJP可抑制肝癌细胞TP 53、CCND 1、p-EGFR、EGF、VEGFA、JUN、IL 6、考克斯-2、AKT 1和MAPK 1的基因表达,而升高ESR 1和CASP 3的表达。综上所述,结果表明YFJP通过介导对HCC相关基因的影响来减弱HCC的进展。
Yangyin Fuzheng Jiedu Prescription (YFJP) is a traditional Chinese medicine (TCM) indicated for the treatment of hepatocellular carcinoma (HCC). Its potential targets and molecular mechanisms are not clear. Therefore, this study intends to explore the molecular mechanism of YFJP based on network pharmacology analysis and in vitro validation. Through univariate and multivariate analyses and survival analysis in HCC patients with or without YFJP treatment we found that drinking alcohol, alfafeto protein ≥ 400 ng/l, baseline portal vein tumor thrombus and total bilirubin level ≥ 18.8 μM) were independent risk factors for poor prognosis, while red blood cell count ≥ 4 × 109/l and TCM treatment were independent protective factors. Besides, YFJP prolonged the cumulative survival of HCC patients. Using online pharmacological methods, we obtained 58 relevant compounds and molecular 53 targets. By using scratch test, Transwell assay, EdU assay, and TUNEL staining, we found that YFJP-containing serum repressed the migration, invasion and proliferation of HCC cells in vitro, and induced cell apoptosis. Moreover, YFJP diminished the gene expression of TP53, CCND1, p-EGFR, EGF, VEGFA, JUN, IL6, COX-2, AKT1, and MAPK1 in HCC cells, but elevated the expression of ESR1 and CASP3. Taken together, results showed that YFJP attenuated HCC progression through mediating effects on HCC-related genes.
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期刊: ONCOLOGY REPORTS
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