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1.哈尔滨商业大学药物工程技术研究中心,哈尔滨 150076
2.哈尔滨商业大学药学院,哈尔滨 150076
研究员,博士。研究方向:抗肿瘤天然药物。E-mail:zouxiang@hrbcu.edu.cn
教授,博士生导师,博士。研究方向:中药炮制。 E-mail:qiuqiuqu@163.com
收稿日期:2022-11-03,
修回日期:2023-02-23,
纸质出版日期:2023-04-30
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邹翔,舒淇,吴双,等.白屈菜-元胡药对抗雌激素受体阳性乳腺癌药效物质及作用机制[J].中国药房,2023,34(08):935-940.
ZOU Xiang,SHU Qi,WU Shuang,et al.Pharmacodynamic substances and mechanism of Chelidonii Herba-Corydalis Rhizoma against estrogen receptor-positive breast cancer[J].ZHONGGUO YAOFANG,2023,34(08):935-940.
邹翔,舒淇,吴双,等.白屈菜-元胡药对抗雌激素受体阳性乳腺癌药效物质及作用机制[J].中国药房,2023,34(08):935-940. DOI: 10.6039/j.issn.1001-0408.2023.08.08.
ZOU Xiang,SHU Qi,WU Shuang,et al.Pharmacodynamic substances and mechanism of Chelidonii Herba-Corydalis Rhizoma against estrogen receptor-positive breast cancer[J].ZHONGGUO YAOFANG,2023,34(08):935-940. DOI: 10.6039/j.issn.1001-0408.2023.08.08.
目的
2
分析白屈菜-元胡药对(CHCR)的主要成分,预测其抗雌激素受体(ER)阳性乳腺癌的药效物质、潜在作用靶点及通路并进行验证。
方法
2
采用超高效液相色谱-四极杆飞行时间串联质谱(UPLC-Q-TOF-MS/MS)技术对CHCR乙醇提取物的成分进行分析;对所得成分进行网络药理学分析,构建CHCR“活性成分-靶点-通路”网络,并对富集通路进行体外细胞实验验证。
结果
2
共鉴定出58个化学成分,含生物碱57个、有机酸1个。网络药理学共筛选出活性成分38个,“成分-疾病”交集靶点的蛋白质-蛋白质互作网络中有核心靶点38个;得基因本体条目258个,京都基因与基因组百科全书通路137条,主要包括雌激素信号通路、磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路等。验证实验结果显示,CHCR作用于MCF-7细胞的半数抑制浓度为693 μg/mL;150、300、600 μg/mL的CHCR可显著降低磷酸化PI3K、磷酸化Akt、ERα蛋白和ESR1 mRNA的表达水平(
P
<0.01)。
结论
2
CHCR抗ER阳性乳腺癌的作用可能与调控ER、PI3K/Akt通路有关,具有多成分、多靶点的作用特点。
OBJECTIVE
2
To analyze the main components of Chelidonii Herba-Corydalis Rhizoma (CHCR), and to predict pharmacodynamic substances against estrogen receptor (ER) -positive breast cancer and their potential targets and signaling pathways, followed by verifying experiments.
METHODS
2
The ethanol extract of CHCR was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS/MS). The network pharmacology analysis was performed for the screened components. The network diagram of CHCR “active components-target-pathway” was constructed, and the enrichment pathway
in vitro
was validated.
RESULTS
2
A total of 58 chemical components were identified, including 57 alkaloids and 1 organic acid. A total of 38 active ingredients were screened from the network pharmacology, and 38 core targets were found in the protein-protein interaction network of “component-disease” intersection targets; 258 gene ontology entries and 137 Kyoto encyclopedia of genes and genomics pathways were obtained, mainly including estrogen signal pathway, phosphatidylinositol-3-kinase/protein kinase B (PI3K/Akt) signal pathway, etc. The results of validation test showed that the median inhibitory concentration of CHCR to MCF-7 cells was 693 μg/mL; 150, 300, 600 μg/mL
CHCR could significantly reduce the expressions of phosphorylated PI3K, phosphorylated Akt, ERα protein and ESR1 mRNA (
P
<0.01).
CONCLUSIONS
2
The anti-ER-positive breast cancer effect of CHCR may be related to the regulation of ER and PI3K/Akt pathways, which has the characteristics of multi-component and multi-target effects.
FERLAY J , COLOMBET M , SOERJOMATARAM I , et al . Cancer statistics for the year 2020:an overview [J ] . Int J Cancer , 2021 .
NUNNERY S E , MAYER I A . Targeting the PI3K-AKT/mTOR pathway in hormone-positive breast cancer [J ] . Drugs , 2020 , 80 ( 16 ): 1685 - 1697 .
SPRING L M , GUPTA A , REYNOLDS K L , et al . Neoadjuvant endocrine therapy for estrogen receptor-positive breast cancer:a systematic review and meta-analysis [J ] . JAMA Oncol , 2016 , 2 ( 11 ): 1477 - 1486 .
GARCIA-MARTINEZ L , ZHANG Y S , NAKATA Y , et al . Epigenetic mechanisms in breast cancer therapy and resistance [J ] . Nat Commun , 2021 , 12 ( 1 ): 1786 .
赵丹妮 , 闫石 , 蔡莉 . 乳腺癌随访和药物副作用管理策略的研究进展 [J ] . 实用肿瘤学杂志 , 2022 , 36 ( 4 ): 369 - 373 .
张青 . 名老中医方药心得丛书:郁仁存常用抗肿瘤药对 [M ] . 北京 : 科学出版社 , 2017 , 120 - 123 .
国家药典委员会 . 中华人民共和国药典:一部 [S ] .2020年版. 北京 : 中国医药科技出版社 , 2020 , 112 - 145 .
蒋姝亭 , 张红波 , 谈胤求 , 等 . 白屈菜碱通过抑制核因子-κB信号促进乳腺癌MCF-7细胞凋亡 [J ] . 中华实验外科杂志 , 2022 , 39 ( 5 ): 862 - 864 .
张蕾 , 王敏 , 张新新 , 等 . 基于网络药理学和分子对接技术分析白屈菜红碱抗乳腺癌的作用机制 [J ] . 西安交通大学学报(医学版) , 2021 , 42 ( 4 ): 554 - 561,573 .
XU Z T , CHEN X P , ZHANG Q W , et al . Corydalis yanhusuo W.T. Wang extract inhibits MCF-7 cell proliferation by inducing cell cycle G2/M arrest [J ] . Am J Chin Med , 2011 , 39 ( 3 ): 579 - 586 .
XU Z T , CHEN X P , FU S , et al . Dehydrocorydaline inhibits breast cancer cells proliferation by inducing apop-tosis in MCF-7 cells [J ] . Am J Chin Med , 2012 , 40 ( 1 ): 177 - 185 .
SHENG P , XIE J , WU Y Q , et al . A network pharmaco-logy approach for uncovering the mechanism of ‘kou-chuangling’ in radiation-induced oral mucositis treatment [J ] . Comb Chem High Throughput Screen , 2023 , 26 ( 5 ): 1042 - 1057 .
SAI C M , WANG J A , LI B J , et al . Isolation and identification of alkaloids from Macleaya microcarpa by UHPLC- Q-TOF-MS and their cytotoxic activity in vitro ,antiangiogenic activity in vivo [J ] . BMC Chem , 2020 , 14 ( 1 ): 5 .
XIA X H , HE J C , LIU B , et al . Targeting ERα degradation by L-tetrahydropalmatine provides a novel strategy for breast cancer treatment [J ] . Int J Biol Sci , 2020 , 16 ( 12 ): 2192 - 2204 .
WANG Y , LIU Y F , DU X Y , et al . Berberine reverses doxorubicin resistance by inhibiting autophagy through the PTEN/Akt/mTOR signaling pathway in breast cancer [J ] . Onco Targets Ther , 2020 , 13 : 1909 - 1919 .
张月 . 白屈菜碱逆转人乳腺癌MCF-7/ADR细胞耐药的机制研究 [D ] . 哈尔滨 : 哈尔滨商业大学 , 2020 .
LIN W J , HUANG J J , YUAN Z W , et al . Protein kinase C inhibitor chelerythrine selectively inhibits proliferation of triple-negative breast cancer cells [J ] . Sci Rep , 2017 , 7 ( 1 ): 2022 .
DING J L , WANG X N , ZHANG Y , et al . Inhibition of BTF3 sensitizes luminal breast cancer cells to PI3Kα inhibition through the transcriptional regulation of ERα [J ] . Cancer Lett , 2019 , 440/441 : 54 - 63 .
LIU Y F , MA H , WANG Y , et al . Cystatin SN affects cell proliferation by regulating the ERα/PI3K-AKT/ERα loopback pathway in breast cancer [J ] . Onco Targets Ther , 2019 , 12 : 11359 - 11369 .
RIBAS R , PANCHOLI S , GUEST S K , et al . AKT antagonist AZD5363 influences estrogen receptor function in endocrine-resistant breast cancer and synergizes with fulvestrant(ICI182780) in vivo [J ] . Mol Cancer Ther , 2015 , 14 ( 9 ): 2035 - 2048 .
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