三阴方治疗三阴性乳腺癌的临床疗效与药理学研究

郝志晔 卢雯平 钱伟 崔莎莎

摘要 目的：探討三阴方治疗晚期三阴性乳腺癌（TNBC）的临床疗效、活性成分及作用机制。方法：选取2018年3月至2019年10月中国中医科学院广安门医院收治的Ⅳ期TNBC患者52例作为研究对象，均给予三阴方，每日1剂，观察患者的无进展生存期（PFS）和临床疗效。依托中药系统药理学数据库与分析平台（TCMSP）检索并筛选三阴方的有效成分和作用靶标，应用GeneGards数据库对三阴性乳腺癌靶标进行检索进而构建成分靶点网络、构建蛋白质-蛋白质相互作用（PPI）网络，并对靶标进行基因本体（GO）功能富集分析、京都基因与基因组百科全书（KEGG）通路富集分析，构建靶点-通路网络图。结果：经三阴方治疗后，患者的中位PFS为（8.64±1.87）个月，客观缓解率为34.6%，疾病控制率为82.7%，卡氏评分和FACT-B评分均有改善，疗效显著。网络药理学研究共筛选出三阴方与三阴性乳腺癌重合靶标110个，GO及KEGG富集分析预测出与疾病相关的多条作用通路。结论：三阴方是治疗晚期三阴性乳腺癌的有效方剂，可延长患者的PFS，提高临床疗效及生命质量。本研究预测三阴方治疗晚期三阴性乳腺癌的主要活性成分为黄酮类及甾醇类化合物，主要调节靶标是AKT1、MAPK1、RELA，可能通过作用于PI3K-AKT、TNF、p53等信号通路对晚期三阴性乳腺癌起到治疗作用。

关键词 三阴方;治疗;晚期;三阴性乳腺癌;临床疗效;药理学研究;活性;作用机制

Clinical Research and Pharmacology Study on Sanyin Decoction in the Treatment of Triple-Negative Breast Cancer

HAO Zhiye，LU Wenping，QIAN Wei，CUI Shasha

（Guanganmen Hospital，China Academy of Chinese Medical Sciences，Beijing 100053，China）

Abstract Objective：To explore the clinical effect，active ingredients and action mechanism of Sanyin Decoction in the treatment of advanced triple-negative breast cancer.Methods：A total of 52 cases of stage IV triple-negative breast cancer patients were selected as the research objects and were given Sanyin Decoction，one dose a day.The progress-free survival（PFS） and clinical effect of the patients were observed.Based on TCMSP，we searched and screened the effective components and targets of Sanyin Decoction.The triple-negative breast cancer targets were searched in the GeneGards database and then the component target network and protein interaction（PPI） network were constructed.The target was analyzed by go function enrichment，KEGG pathway enrichment and the target pathway network map was constructed.Results：The median PFS were 8.64±1.87 months，the objective remission rate and the disease control rate were 34.6% and 82.7%，respectively after the treatment with Sanyin Decoction.Both the casabella score and the FACT-B score were improved significantly，showing significant curative effect.A total of 110 overlapping targets of Sanyin Decoction and triple-negative breast cancer were selected by network pharmacology research.Go and KEGG enrichment analysis predicted multiple disease-related pathways.Conclusion：Sanyin Decoction is an effective prescription for the treatment of advanced triple negative breast cancer，which can improve prolong PFS，the clinical efficacy，and improve quality of life in advanced triple-negative breast cancer patients.This study predicts that the main active components of Sanyin Decoction in the treatment of advanced triple-negative breast cancer are mainly flavonoids and sterols，the main regulatory targets are AKT1，MAPK1，RELA，which might be related to PI3K-AKT，TNF，p53 and so on signal pathway and plays a therapeutic role in advanced triple-negative breast cancer.

Keywords Sanyin Decoction; Treatment; Advanced; Triple-negative breast cancer; Clinical efficacy; Pharmacology research; Active ingredients; Action mechanism

中图分类号：R289.5;R966文献标识码：Adoi：10.3969/j.issn.1673-7202.2021.16.023

乳腺癌是世界上女性最多发的恶性肿瘤，在全球女性恶性肿瘤中居首位，严重危害女性健康[1]。……