夏枯草全草及其活性成分对人乳腺癌MDA-MB-231细胞增殖、凋亡的作用及机制  

Effect of Prunella sinensis and its active components on proliferation andapoptosis of human breast cancer MDA-MB-231 cells and its mechanism

作　　者：陶然然 蔡杭 吕文亮 胡俊杰 郑国华 吴勇 TAO Ran-ran;CAI Hang;LYU Wen-liang;HU Jun-jie;ZHENG Guo-hua;WU Yong(Pharmacy School,Hubei University of Chinese Medicine,Wuhan 430065,China;Key Laboratory of Chinese Medicine Resource and Compound Prescription,Hubei University of Chinese Medicine,Wuhan 430065,China)

机构地区：[1]湖北中医药大学药学院,湖北武汉430065 [2]湖北中医药大学中药资源与中药复方教育部重点实验室,湖北武汉430065

出　　处：《中国药理学通报》2025年第2期373-382,共10页Chinese Pharmacological Bulletin

基　　金：湖北省科技重大专项项目(No 2020ACAO19-04)。

摘　　要：目的研究夏枯草全草及其活性成分对乳腺癌恶性进展的影响及其机制。方法构建乳腺癌移植瘤模型,随机分为模型组、夏枯草全草低、中、高剂量组(0.1、0.2、0.4 g·mL^(-1))、紫杉醇组(10 mg·kg^(-1)),连续给药28 d后收集组织。检测各组裸鼠体质量、肿瘤体积和质量,HE和IHC观察病理切片。采用CCK-8法、流式周期与凋亡检测全草乙酸乙酯萃取物对MDA-MB-231细胞增殖、周期及凋亡的影响。Western blot检测增殖与凋亡相关蛋白的表达水平。采用UPLCQ-TOFMS/MS检测夏枯草全草乙酸乙酯萃取物化学成分。结果夏枯草全草能明显抑制人乳腺癌裸鼠移植瘤的生长(P<0.05);促进肿瘤细胞凋亡;抑制肿瘤细胞向肝肺的转移;对肝脏和脾脏起到保护;降低了肿瘤细胞中Ki-67与CK17的表达。全草乙酸乙酯萃取物可抑制乳腺癌MDA-MB-231细胞增殖(P<0.01);将细胞阻滞在S期,促进细胞凋亡(P<0.01);Western blot结果显示,全草乙酸乙酯萃取物促进Bax、cleaved caspase-3、cleaved caspase-9蛋白的表达,抑制Bcl-2、Caspase-3、Caspase-9、CyclinA2、CDK2蛋白的表达(P<0.05,P<0.01)。UPLCQ-TOF MS/MS从夏枯草全草乙酸乙酯萃取物中鉴别出51种化合物。结论夏枯草全草及其活性成分通过抑制乳腺癌细胞增殖,促进细胞凋亡等机制从而抑制乳腺癌的发展。Aim To study the effects of whole herb of Prunella and its active components on the malignant progression of breast cancer and its mechanism.Methods Breast cancer transplantation tumor model was constructed and randomly divided into the model group,low,medium and high dose group of whole herb of Prunella(0.1,0.2,0.4 g·mL^(-1) by gavage)and paclitaxel(10 mg·kg^(-1) by intraperitoneal injection),which was administered by gavage every day,and the tumor tissues were collected after 28 days of intervention.The weight,tumor volume and mass of nude mice in each group were detected,HE staining was used to observe the morphology of breast cancer tumor tissues,and immunohistochemical staining was used to observe the proliferation of cell-cycle regulatory protein-67(Ki-67)and cytokeratin 17(CK17)in breast cancer tumor tissues.The cellular experiments were performed by using different concentrations of the ethyl acetate extract of the whole herb of Prunella in breast cancer MDA-MB-231 cells for 24 h.The proliferation of MDA-MB-231 cells and the effects on the cell cycle and apoptosis of MDA-MB-231 cells were detected by using the CCK-8 assay,the cell cycle flow and the apoptotic cell flow.Western blot was used to detect the effect of ethyl acetate extract of whole herb of Prunella on the expression of apoptosis-related proteins in breast cancer MDA-MB-231 cells.UPLCQ-TOF MS/MS was used to detect the chemical compositions of the ethyl acetate extract of Prunella whole herb.Results The whole herb of Prunella had no significant effect on the growth of nude mice(P>0.05);it could significantly inhibit the growth of transplanted tumors in nude mice with human breast cancer(P<0.05);the results of HE staining showed that the cells in the tissues appeared to be relatively sparse with the increase of the dose of Prunella and had different degrees of nuclear consolidation and deep staining of nuclei and the apoptosis of the tumor cells increased;the metastasis of tumor cells to the liver and lungs was inhibited,when compared with tha

关 键 词：夏枯草全草 移植瘤 乳腺癌细胞 增殖 凋亡 UPLCQ-TOF MS/MS 

分 类 号：R-332[医药卫生] R287.71R284.1R329.25R329.28R737.9