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作 者:耿子翔 刘莹 聂小丽 井方圆 陈海阳 张开勇 刘鹏 袁龙 李冰融 刘特[3] 张必萌 GENG Zi-xiang;LIU Ying;NIE Xiao-li;JING Fang-yuan;CHEN Hai-yang;ZHANG Kai-yong;LIU Peng;YUAN Long;LI Bing-rong;LIU Te;ZHANG Bi-meng(Shanghai University of Traditional Chinese Medicine,Shanghai 201203;Department of Dermatology,Central Hospital of Songjiang District,Shanghai 201699;Shanghai Institute of Chinese Medicine for Geriatric,Shanghai University of Traditional Chinese Medicine,Shanghai 200030;Department of Acupuncture,Shanghai General Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai 200080)
机构地区:[1]上海中医药大学,上海201203 [2]上海市松江区中心医院皮肤科,上海201699 [3]上海市中医老年医学研究所,上海200030 [4]上海交通大学医学院附属第一人民医院针灸科,上海200080
出 处:《中南药学》2022年第12期2786-2792,共7页Central South Pharmacy
基 金:上海市科委中医引导类项目(No.18401903100)。
摘 要:目的基于动物实验和网络药理学探讨子芪抑瘤饮治疗卵巢癌的潜在机制。方法动物实验观察子芪抑瘤饮对皮下成瘤的影响,利用HE染色观察瘤体的形态学改变;通过生物信息学技术进行基因富集分析;利用免疫组织化学染色检测Ki67、TP53、ESR1、EGFR、VEGFA的蛋白表达水平。结果子芪抑瘤饮能显著减小卵巢癌瘤体的体积和质量(P<0.05),上皮细胞异型性和病理性核分裂象减少。通过数据库共检索到子芪抑瘤饮的154个活性成分,283个潜在靶点,药物与疾病交集靶点38个。PPI网络分析以及GO和KEGG通路富集分析得到TP53、ESR1、AKT1、EGFR等10个核心靶点,分子功能主要为分子结合、催化活性等,生物学进程主要为分子代谢、刺激反应等。免疫组织化学染色显示子芪抑瘤饮显著降低了Ki67、TP53、ESR1的表达(P<0.05)。结论子芪抑瘤饮可能通过槲皮素、木犀草素、山柰酚等关键成分作用于TP53、ESR1等靶点抑制卵巢癌细胞增殖和耐药,促进凋亡等。Objective To explore the potential mechanism of Ziqi Yiliu decoction for ovarian cancer based on animal experiments and network pharmacology.Methods Animal experiments were conducted to observe the effect of Ziqi Yiliu decoction on subcutaneous tumorigenesis.HE staining was used to observe the morphological changes of the tumor.Gene set enrichment analysis was performed with the bioinformatics analysis.Immunohistochemical staining was used to detect the expression level of Ki67,TP53,ESR1,EGFR,and VEGFA.Results Ziqi Yiliu decoction significantly decreased the volume and mass of the ovarian cancer(P<0.05),and reduced nuclear atypia and pathological nuclear division.Totally 154 active components,283 potential targets and 38 drug and disease intersection targets of Ziqi Yiliu decoction were retrieved through the database.PPI network analysis and GO and KEGG pathway enrichment analysis showed that 10 core targets such as TP53,ESR1,AKT1 and EGFR were enriched in the cancer signaling pathways.The molecular functions mainly included molecular binding and catalytic activity,and the biological processes were mainly molecular metabolism and stimulation responses.Immunohistochemical staining showed that Ziqi Yiliu decoction significantly decreased the expression of Ki67,TP53,and ESR1(P<0.05).Conclusion Ziqi Yiliu decoction is effective for ovarian cancer,whose mechanism is through the action of key components such as quercetin,luteolin and kaempferol on TP53,ESR1 and other targets to inhibit the proliferation and drug resistance,thus promoting apoptosis.
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