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[摘要]
目的 研究夏枯草多糖(P)、三萜(T)、挥发油(V)组分及不同配伍(PT、PV、TV、PTV)在小鼠体内抗乳腺癌的活性及作用机制。方法 采用4T1荷瘤小鼠乳腺癌模型,评价夏枯草各组分及配伍的体内抗乳腺癌活性。采用Micro CT检测小鼠乳腺癌肿瘤大小;HE染色法检测乳腺癌组织、各脏器的病理结构变化;TUNEL染色法检测肿瘤组织的凋亡指数;免疫组化法检测增殖细胞核抗原(PCNA)、CD-31、E-cadherin蛋白表达;Elisa试剂盒检测血清雌二醇含量。结果 与模型组比较,T和PTV可显著抑制4T1荷瘤小鼠肿瘤的生长与大小,具体表现为T和PTV组荷瘤小鼠肿瘤组织炎症细胞浸润、变性性坏死,肿瘤细胞凋亡;其机制可能为T和PTV可降低雌激素的含量,下调PCNA蛋白的表达,抑制荷瘤小鼠肿瘤细胞增殖;下调CD-31蛋白的表达,减少肿瘤组织内血管生成;上调E-cadherin蛋白的表达,抑制肿瘤细胞转移。结论 T和PTV具有显著的抗肿瘤活性,可以作为抗乳腺癌的候选药物。
[Key word]
[Abstract]
Objective To study antibreast cancer activity and the mechanism of appropriate components of polysaccharides (P), triterpenes (T), the essential oil (V), and different compatibilities (PT, PV, TV, and PTV) of Prunella vulgaris in vivo. Methods 4T1 breast cancer model was established to evaluate anti-breast cancer activity. The appropriate components of P. vulgaris were screened. The tumor volume and the shaded areas in breast cancer mice were detected by living small animal Micro-CT scan. The structural changes of each organ were detected by HE staining. TUNEL staining was used to detect apoptotic rate of tumor. The expression of PCNA, CD-31, and E-cadherin were detected by immunohistochemistry (IHC). Serum estradiol was detected by Elisa kit. Results T and PTV had significant anti-breast cancer activity. There were inflammatory cells infiltration, degeneration and necrosis, tumor cell apoptosis in the T and PTV groups. T and PTV could inhibit cell proliferation by reducing the estradiol level and downregulating the overexpression of PCNA proteins. T and PTV could also reduce tumor angiogenesis by downregulating the protein expression of CD-31. T and PTV also inhibited the metastatic process by upregulating the protein expression of E-cadherin. Conclusion T and PTV showed significant anti-breast cancer activities, suggesting that T and PTV can be a potential drug for breast cancer.
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[基金项目]
国家重点研发计划中医药现代化研究重点专项:苦参等大宗中药材的综合利用技术研究(2017YFC1701900);湖南省自然科学基金项目(2017JJ1023,2017JJ4045,2019JJ50449);湖南省教育厅优秀青年基金(17B198);长沙市科技计划项目(kq1801041,kq1801046);湖南中医药大学中药学一流学科(2018ZYX05)