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熊果酸对IL-6介导的乳腺癌细胞侵袭与迁移的抑制作用 Δ

刘荣荣 ，张 涛，相芬芬，陈自喜，张孟哲，康向东，吴 蓉（上海中医药大学附属普陀医院检验科，上海
＊
#
200062）

中图分类号 R965 文献标志码 A 文章编号 1001-0408（2023）08-0955-06
DOI 10.6039/j.issn.1001-0408.2023.08.12

摘 要 目的 探讨熊果酸对白细胞介素6（IL-6）介导的乳腺癌MDA-MB-231细胞（简称“231细胞”）的侵袭与迁移的抑制作用。
方法 采用CCK-8法检测20、40、80、160、320 µmol/L熊果酸对231细胞增殖率的影响。将细胞分为对照组、模型组和给药组，划痕
实验与Transwell实验检测细胞的迁移能力与侵袭能力；实时荧光定量聚合酶链式反应（q-PCR）法与Western blot法检测细胞上皮
间质转化相关标志物E钙黏蛋白（E-cad）、基质金属蛋白酶2（MMP2）、MMP9、波形蛋白（Vim）、CD44分子（CD44）、醛脱氢酶1家
族成员A1（ALDH1A1）mRNA与蛋白的相对表达情况；Western blot法检测Janus激酶2/信号转导及转录激活因子3（JAK2/STAT3）
通路中JAK2、STAT3的磷酸化水平[以磷酸化JAK2（p-JAK2）/JAK2比值、磷酸化STAT3（p-STAT3）/STAT3比值计]。结果 实验选
取熊果酸低浓度20 µmol/L（对细胞增殖能力无明显抑制作用）作为后续给药浓度。与对照组比较，模型组细胞的迁移、侵袭能力
均显著增强（P＜0.05）；与模型组比较，给药组细胞的迁移、侵袭能力均显著降低（P＜0.05）。与对照组比较，模型组细胞中上皮间
质转化相关标志物MMP9、MMP2、Vim、ALDH1A1、CD44 mRNA与蛋白的相对表达量均有不同程度的升高，E-cad mRNA与蛋白
的相对表达量均有不同程度的降低，部分差异有统计学意义（P＜0.05），p-JAK2/JAK2比值、p-STAT3/STAT3比值均显著升高（P＜
0.05）；与模型组比较，给药组细胞中上述指标的表达均有一定程度逆转。结论 熊果酸通过阻断JAK2/STAT3信号通路的激活进
而抑制炎症因子IL-6诱导的上皮间质转化过程，最终抑制乳腺癌细胞的侵袭、迁移。
关键词 熊果酸；白细胞介素6；乳腺癌；Janus激酶2/信号转导及转录激活因子3通路；侵袭；迁移

Inhibitory effects of ursolic acid on IL-6-mediated invasion and migration of breast cancer cells
LIU Rongrong，ZHANG Tao，XIANG Fenfen，CHEN Zixi，ZHANG Mengzhe，KANG Xiangdong，WU Rong
（Dept. of Laboratory， Putuo Hospital Affiliated to Shanghai University of Traditional Chinese Medicine，
Shanghai 200062， China）

ABSTRACT OBJECTIVE To investigate the inhibitory effects of ursolic acid on interleukin-6 （IL-6）-mediated invasion and
migration of breast cancer MDA-MB-231 cells （hereinafter referred to as “231 cells”）. METHODS The effects of 20， 40， 80， 160
and 320 µmol/L ursolic acid on the proliferation rate of 231 cells were measured by CCK-8 method. The breast cancer 231 cells
were divided into control group， model group and administration group. The migration and invasion abilities of cells were detected
by scratch assay and Transwell assay. Real-time quantitative polymerase chain reaction （q-PCR） assay and Western blot assay were
used to detect the mRNA and protein expressions of epithelial-mesenchymal transition-related makers such as E cadherin （E-cad），
matrix metalloprotein 2 （MMP2）， MMP9， vimentin （Vim）， CD44 molecule （CD44） and aldehyde dehydrogenase 1 family member
A1 （ALDH1A1）. The phosphorylation levels of JAK2 and STAT3 in the Janus kinase 2/signal transducer and activator of transcription
3 （JAK2/STAT3） signaling pathway （in terms of p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio） were detected by Western blot
assay. RESULTS A low concentration of ursolic acid of 20 µmol/L （no significant inhibitory effect on cell proliferation ability）
was selected as the subsequent administration concentration. Compared with the control group， the migration and invasion abilities
of cells in the model group were significantly enhanced （P＜0.05）； compared with the model group， the migration and invasion
abilities of cells in the administered group were significantly reduced （P＜0.05）. Compared with the control group， the relative
mRNA and protein expressions of epithelial-mesenchymal transition-related markers MMP9， MMP2， Vim， ALDH1A1 and CD44
were all elevated to different extents， and the mRNA and protein expressions of E-cad were all decreased to different extents
in the model group cells， and part of the differences had
Δ 基金项目 上海市“医苑新星”青年医学人才培养资助计划项目 statistical significance （P＜0.05）， the p-JAK2/JAK2 ratio and
（No.沪卫计人事〔2019〕72号）；上海市普陀区卫生健康系统科技创新 p-STAT3/STAT3 ratio were significantly increased in the model
项目（No.ptkwws202307）；上海市普陀区中心医院科研启航计划项目
group （P＜0.05）； compared with the model group， the
（No.2022-RCQH-03）
expressions of the above indicators were reversed to some
＊第一作者 硕士研究生。研究方向：中药逆转肿瘤侵袭与转移的
分子机制。E-mail：1064417934@qq.com extent in the administration group. CONCLUSIONS Ursolic
# 通信作者 主任技师，硕士生导师。研究方向：中药逆转肿瘤侵 acid blocks the activation of JAK2/STAT3 signaling pathway
袭与转移的分子机制。E-mail：rong701@126.com and thus inhibits the epithelial-mesenchymal transition induced

中国药房 2023年第34卷第8期 China Pharmacy 2023 Vol. 34 No. 8 · 955 ·