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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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司运辉 ,蒋 凯 ,钱立全 ,陈永顺 ,别会杰(1. 商丘医学高等专科学校解剖与组胚教研室,河南 商丘
476000;2.商丘医学高等专科学校生理学教研室,河南 商丘 476000;3.商丘医学高等专科学校药理学教研室,
河南 商丘 476000)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2024)08-0918-07
DOI 10.6039/j.issn.1001-0408.2024.08.04
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、80 μmol/L 的 Auc),Auc-H+pcDNA-NC 组(80 μmol/L 的 Auc+转染 pcDNA-NC 质粒),Auc-H+pcDNA-CDK1
组(80 μmol/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。
关键词 桃叶珊瑚苷;乳腺癌;恶性生物学行为;CDK1/CCNB1/PLK1信号通路
Effects and mechanism of aucubin on malignant biological behavior of breast cancer cells
SI Yunhui ,JIANG Kai ,QIAN Liquan ,CHEN Yongshun ,BIE Huijie(1. Anatomy and Embryo Teaching and
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Research Office, Shangqiu Medical College, Henan Shangqiu 476000, China;3. Pharmacology Teaching and
Research Office, Shangqiu Medical College, Henan Shangqiu 476000, China)
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
Δ 基金项目 国家卫生健康委医药卫生科技发展研究中心课题
the CDK1/CCNB1/PLK1 signaling pathway.
(No.W2022ZT726);河南省高等学校重点科研项目(No.23B310015)
*第一作者 讲师。研究方向:中药药理。E-mail:yunhuisi@163. KEYWORDS aucubin; breast cancer; malignant biological
com behavior; CDK1/CCNB1/PLK1 signaling pathway
· 918 · China Pharmacy 2024 Vol. 35 No. 8 中国药房 2024年第35卷第8期