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

doi:10.6039/j.issn.1001-0408.2023.08.12

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Inhibitory effects of ursolic acid on IL-6-mediated invasion and migration of breast cancer cells

更新时间：2023-04-25

- Inhibitory effects of ursolic acid on IL-6-mediated invasion and migration of breast cancer cells
- ZHONGGUO YAOFANG Vol. 34, Issue 8, Pages: 955-960(2023)
- 作者机构：
  
  上海中医药大学附属普陀医院检验科，上海　200062
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2023.08.12
  CLC： R965
- Published：30 April 2023，
  
  Received：10 November 2022，
  
  Revised：17 February 2023，
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刘荣荣,张涛,相芬芬等.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[J].中国药房,2023,34(08):955-960.

LIU Rongrong,ZHANG Tao,XIANG Fenfen,et al.Inhibitory effects of ursolic acid on IL-6-mediated invasion and migration of breast cancer cells[J].ZHONGGUO YAOFANG,2023,34(08):955-960.
刘荣荣,张涛,相芬芬等.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[J].中国药房,2023,34(08):955-960. DOI： 10.6039/j.issn.1001-0408.2023.08.12.

LIU Rongrong,ZHANG Tao,XIANG Fenfen,et al.Inhibitory effects of ursolic acid on IL-6-mediated invasion and migration of breast cancer cells[J].ZHONGGUO YAOFANG,2023,34(08):955-960. 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（

＜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（

＜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（

＜0.05），p-JAK2/JAK2比值、p-STAT3/STAT3比值均显著升高（

＜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。

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 （

＜0.05）； compared with the model group， the migration and invasion abilities of cells in the administered group were significantly reduced （

＜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 statistical significance （

＜0.05）， the p-JAK2/JAK2 ratio and p-STAT3/STAT3 ratio were significantly increased in the model group （

＜0.05）； compared with the model group， the expressions of the above indicators were reversed to some extent in the administration group.

CONCLUSIONS

Ursolic acid blocks the activation of JAK2/STAT3 signaling pathway and thus inhibits the epithelial-mesenchymal transition induced by the inflammatory factor IL-6， which ultimately interrupts the invasion and metastasis of breast cancer cells.

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

Keywords

IL-6breast cancerJAK2/STAT3 pathwayinvasionmigration

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