基于网络药理学和动物实验探讨槲皮素干预具抑郁特征乳腺癌的作用机制

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中文摘要：[目的]探讨槲皮素对具抑郁特征乳腺癌的治疗作用及机制.[方法]采用网络药理学和生物信息学的方法,预测槲皮素治疗具抑郁特征乳腺癌的关键靶点和作用机制.通过动物实验验证预测得到的结果:构建具抑郁特征乳腺癌小鼠模型,分组后进行槲皮素干预治疗,采用旷场试验评价小鼠的抑郁情绪,测量肿瘤体积、肿瘤质量,采用免疫组织化学染色法检测肿瘤组织Ki-67表达,采用Western Blot法检测肿瘤组织肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、p53、半胱氨酸天冬氨酸蛋白酶3(Caspase-3)、B细胞淋巴瘤/白血病2(Bcl-2)表达,末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记(TUNEL)法检测肿瘤组织细胞凋亡.[结果]具抑郁特征乳腺癌模型组小鼠旷场试验总运动路程、旷场试验中央区停留时间比减小,肿瘤体积、肿瘤质量升高,肿瘤组织Ki-67表达水平显著升高,肿瘤组织TNF-α、IL-6、p53、Caspase-3表达量下降且Bcl-2表达量增加,TUNEL阳性细胞率降低,与对照组比较,差异均有统计学意义(P＜0.01或P＜0.001);与模型组比较,槲皮素组上述指标均得到显著逆转(P＜0.01或P＜0.001)＜[结论]槲皮素可有效抑制小鼠具抑郁特征乳腺癌的进展,其机制与调控TNF、IL6、TP53、CASP3、BCL2等靶点进而促进肿瘤细胞凋亡有关.

外文标题：Study on the Mechanism of Quercetin Intervention in Breast Cancer with Depressive Characteristics Based on Network Pharmacology and Animal Experiments

外文摘要：Objective To explore the mechanism of quercetin in the treatment of breast cancer with depressive features using network pharmacology and animal experiments.Methods Network pharmacology and bioinformatics methods were used to predict the key targets and mechanisms of quercetin in the treatment of breast cancer with depressive characteristics.The predicted results were verified by animal experiments.A mouse model of breast cancer with depressive characteristics was constructed,and quercetin intervention was performed after grouping.The depression of mice was evaluated by open field test.The tumor volume and tumor mass were measured.The expression of Ki-67 in tumor tissue was detected by immunohistochemical staining.The expressions of tumor necrosis factor α(TNF-α),interleukin 6(IL-6),p53,Caspase-3 and B-cell lymphoma/leukemia 2(Bcl-2)in tumor tissue were detected by Western Blot.Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)method was used to detect the apoptosis of tumor cells.Results In the breast cancer model group with depressive characteristics,the total movement distance in the open field test and the ratio of residence time in the central area of the open field test were decreased,the tumor volume and tumor mass were significantly increased,and Ki-67 expression level in the tumor tissue was significantly increased,the expression levels of TNF-α,IL-6,p53 and Caspase-3 in the tumor tissue were decreased and the expression level of Bcl-2 was increased,as well as the rate of TUNEL positive cells was decreased,the differences being statistically significant compared with the control group(P＜0.01 or P＜0.001).Compared with the model group,the above indexes were significantly reversed in the quercetin group(P＜0.01 or P＜0.001).Conclusion Quercetin can effectively inhibit the progression of breast cancer with depressive characteristics in mice,and its mechanism is related to the regulation of TNF,IL6,TP53,CASP3,BCL2 and other targets to promote tumor cell apoptosis.

外文关键词：

quercetinbreast cancerdepressionapoptosisnetwork pharmacologyexperimental verificationmice

作者：

吴迎朝、梁裕琪、胡玉宇、陈柳汕、吴芃、左谦、陈前军

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作者单位：

广州中医药大学第二临床医学院,广东广州 510405

广州中医药大学第二附属医院中医证候全国重点实验室,广东广州 510120

广东省中医院乳腺科,广东广州 510120

广东省中医药科学院,广东广州 510120

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关键词：

槲皮素乳腺癌抑郁细胞凋亡网络药理学实验验证小鼠

基金：

国家自然科学基金资助项目国家自然科学基金资助项目国家自然科学基金资助项目广东省自然科学基金资助项目广东省自然科学基金资助项目广州市科技计划项目广州市科技计划项目广东省中医院中医药科技专项科研项目广东省中医证候临床研究重点实验室项目中医湿证国家重点实验室自主项目

项目编号：

8197457182274513823052342020A151107602023A1515011115SL2023A03J01120SL2023A04J00228YN2022QN32YN2023ZH10QZ2023ZZ13

出版年：

2024

DOI：

10.13359/j.cnki.gzxbtcm.2024.10.039

广州中医药大学学报

广州中医药大学

广州中医药大学学报

CSTPCD

影响因子：1.055

ISSN：1007-3213

年,卷(期)：2024.41(10)