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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;2.  Physiology  Teaching  and
          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
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