桃叶珊瑚苷对乳腺癌细胞恶性生物学行为的影响及机制
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篇名: | 桃叶珊瑚苷对乳腺癌细胞恶性生物学行为的影响及机制 |
TITLE: | Effects and mechanism of aucubin on malignant biological behavior of breast cancer cells |
摘要: | 目的 探讨桃叶珊瑚苷(Auc)调节周期蛋白依赖性激酶1(CDK1)/周期蛋白B1(CCNB1)/Polo样激酶1(PLK1)信号通路对乳腺癌细胞恶性生物学行为的影响。方法以人乳腺癌细胞MCF-7为对象,将其分为对照组,Auc低、中、高浓度组(Auc-L、Auc-M、Auc-H组,20、40、80μmol/L的Auc),Auc-H+pcDNA-NC组(80μmol/L的Auc+转染pcDNA-NC质粒),Auc-H+pcDNA-CDK1组(80μmol/L的Auc+转染pcDNA-CDK1质粒),检测各组细胞的增殖、克隆形成、侵袭、迁移能力,凋亡情况及周期分布,凋亡、上皮-间充质转化(EMT)、CDK1/CCNB1/PLK1信号通路相关蛋白的表达情况。以BALB/c裸鼠为对象,通过皮下接种MCF-7细胞悬液建立移植瘤模型,并将其分为对照组和Auc组(每组12只),检测各组裸鼠肿瘤体积、质量及肿瘤组织中CDK1/CCNB1/PLK1信号通路相关蛋白的表达情况。结果与对照组细胞相比,Auc各浓度组的细胞克隆形成数、增殖率、细胞侵袭数、划痕愈合率、G1/G0期和S期细胞占比以及B细胞淋巴瘤2(Bcl-2)、神经钙黏素、纤维连接蛋白、CDK1、CCNB1、PLK1蛋白的表达水平均显著降低(P<0.05),细胞凋亡率、G2/M期细胞占比以及Bcl-2相关X蛋白、上皮钙黏素蛋白的表达水平均显著增加(P<0.05),呈浓度依赖性(P<0.05);与Auc-H+pcDNA-NC组细胞相比,Auc-H组细胞上述指标的差异均无统计学意义(P>0.05),而Auc-H+pcDNA-CDK1组细胞上述指标则显著逆转(P<0.05)。与对照组裸鼠相比,Auc组裸鼠肿瘤体积、质量以及肿瘤组织中CDK1、CCNB1、PLK1蛋白的表达水平均显著降低(P<0.05)。结论Auc能抑制乳腺癌细胞的增殖、侵袭和迁移,诱导细胞周期阻滞,抑制EMT进程,该作用可能与抑制CDK1/CCNB1/PLK1信号通路激活有关。 |
ABSTRACT: | OBJECTIVE To investigate the effects of aucubin (Auc) on the malignant biological behavior of breast cancer cells by regulating cyclin-dependent kinase 1(CDK1)/cyclin B1(CCNB1)/Polo-like kinase 1 (PLK1) signaling pathway. METHODS Human breast cancer cells MCF-7 were divided into control group, Auc low-, medium- and high-concentration groups (AUC-L, AUC-M, AUC-H groups, 20, 40 and 80 μmol/L Auc), Auc-H+pcDNA-NC group (80 μmol/L Auc+transfected pcDNA- NC plasmid), and Auc-H+pcDNA-CDK1 group (80 μmol/L Auc+transfected pcDNA-CDK1 plasmid). Cell proliferation, clonal formation, invasion and migration abilities, apoptosis and cycle distribution, and the expressions of related proteins of apoptosis, epithelial-mesenchymal transformation (EMT) and CDK1/CCNB1/PLK1 signaling pathway were detected in each group. The transplanted tumor model of BALB/c nude mice was established by subcutaneous inoculation of MCF-7 cell suspension, and the mice were divided into control group and Auc group (12 mice in each group). The tumor volume, mass and the expressions of related proteins of CDK1/CCNB1/PLK1 signaling pathway in tumor tissues were detected. RESULTS Compared with control group, the number of clonal formation, proliferation rate, cell invasion number, scar healing rate, G1/G0 phase and S phase cell proportions, and the expressions of B cell lymphoma-2 (Bcl-2), N-cadherin, fibronectin, CDK1, CCNB1 and PLK1 were decreased significantly (P<0.05). The apoptotic rate, G2/M phase cell proportion and the expressions of Bcl-2 associated X protein and E-cadherin were significantly increased, in a dose-dependent manner (P<0.05). Compared with the Auc-H+pcDNA-NC group, there was no statistical significance in the above indexes in the Auc-H group (P>0.05), while the above indexes in the Auc-H+ pcDNA-CDK1 group were significantly reversed (P<0.05). Compared with the control group, the tumor volume and mass, and the expressions of CDK1, CCNB1 and PLK1 in tumor tissue of Auc group were significantly decreased (P<0.05). CONCLUSIONS Auc can inhibit the proliferation, invasion and migration of breast cancer cells, induce cell cycle arrest, and inhibit the progression of EMT, which may be related to inhibiting the activation of the CDK1/CCNB1/PLK1 signaling pathway. |
期刊: | 2024年第35卷第08期 |
作者: | 司运辉;蒋凯;钱立全;陈永顺;别会杰 |
AUTHORS: | SI Yunhui,JIANG Kai,QIAN Liquan,CHEN Yongshun,BIE Huijie |
关键字: | 桃叶珊瑚苷;乳腺癌;恶性生物学行为;CDK1/CCNB1/PLK1信号通路 |
KEYWORDS: | aucubin; breast cancer; malignant biological |
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