Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis

Yan-min LI; Xue-qing WU; Hua WAN; Shi-jun SHAO; Si-qi DING

doi:10.13422/j.cnki.syfjx.20201977

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Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis

Pharmacology | 更新时间：2020-12-10

- Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 26, Issue 23, Pages: 106-112(2020)
- 作者机构：
  
  上海中医药大学附属曙光医院，上海 200021
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20201977
  CLC： R22;R242;R2-031;R285.5
- Received：09 March 2020，
  
  Published Online：24 July 2020，
  
  Published：05 December 2020
- 稿件说明：
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李艳敏,吴雪卿,万华等.乳癌术后方通过SDF-1/CXCR4生物轴对MDA-MB-453乳腺癌细胞增殖和转移的影响[J].中国实验方剂学杂志,2020,26(23):106-112.

LI Yan-min,WU Xue-qing,WAN Hua,et al.Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(23):106-112.
李艳敏,吴雪卿,万华等.乳癌术后方通过SDF-1/CXCR4生物轴对MDA-MB-453乳腺癌细胞增殖和转移的影响[J].中国实验方剂学杂志,2020,26(23):106-112. DOI： 10.13422/j.cnki.syfjx.20201977.

LI Yan-min,WU Xue-qing,WAN Hua,et al.Effect of Ru′ai Shuhou Prescription on Proliferation and Metastasis of Breast Cancer MDA-MB-453 Cells Through SDF-1/CXCR4 Biological Axis[J].Chinese Journal of Experimental Traditional Medical Formulae,2020,26(23):106-112. DOI： 10.13422/j.cnki.syfjx.20201977.

摘要

目的

以基质细胞衍生因子-1（Stromal cell-derived factor-1，SDF-1）/趋化因子受体4（Chemokine receptor，CXCR4）生物轴为基础，探讨乳癌术后含药血清对乳腺癌细胞MDA-MB-453增殖和侵袭能力的影响。

方法

建立SDF-1诱导的CXCR4高表达MDA-MB-453细胞模型，制备乳癌术后方含药血清及空白大鼠血清。实验分空白组，空白大鼠血清组，SDF-1+空白大鼠血清组，SDF-1+乳癌术后方组，AMD3100+SDF-1+空白大鼠血清组和AMD3100+SDF-1+乳癌术后方组。干预48 h，采用cell counting kit-8（CCK-8）法检测细胞增殖情况，transwell小室实验检测细胞侵袭能力，分别用实时荧光定量聚合酶链式反应（Real-time PCR）和蛋白免疫印迹法（Western blot）检测细胞CXCR4，基质金属蛋白酶（matrix metalloproteinase，MMP）-2，MMP-9 mRNA及蛋白表达情况。

结果

与空白血清组比较，SDF-1为100 μg·L

-1

时，MDA-MB-453细胞增殖明显，CXCR4 mRNA表达明显增加（

0.05）；与SDF-1+空白大鼠血清组比较，乳癌术后方能抑制SDF-1诱导的MDA-MB-453细胞增殖、侵袭行为，下调CXCR4，MMP-2，MMP-9 mRNA和蛋白表达水平（

0.05）；经AMD3100预处理24 h，乳癌术后方对MDA-MB-453细胞增殖的抑制作用明显增强（

0.05）；同时，乳癌术后方下调CXCR4，MMP-2，MMP-9 mRNA和蛋白表达的作用明显增加（

0.05）。

结论

乳癌术后方可通过调控SDF-1/CXCR4生物轴，降低MDA-MB-453细胞MMP-2，MMP-9表达，减少细胞外基质（extracellular matrix，ECM）降解，进而抑制乳腺癌细胞转移的发生；与CXCR4抑制剂AMD3100具有协同效应。

Abstract

Objective

To investigate the effect of Ru′ai Shuhou prescription （RSR） drug-containing serum on the proliferation and invasion ability of breast cancer cells MDA-MB-453 based on the biological axis of stromal cell-derived factor-1（SDF-1）/chemokine receptor 4 （CXCR4）.

Method

A model of MDA-MB-453 cells with SDF-1-induced high expression of CXCR4 was established， and the rat drug-serum containing RSR and blank rat serum were prepared respectively. The cells were divided into fetal bovine serum control group （Blank）， blank rat serum group， SDF-1+blank rat serum group， SDF-1+RSR group， AMD3100+ SDF-1+blank rat serum group， and AMD3100+ SDF-1+RSR group. After intervention for 48 h， cell proliferation was detected by cell counting kit-8 （CCK-8） assay， cell invasion ability was detected by transwell assay， and mRNA and protein expressions of CXCR4， matrix metalloproteinase-2 （MMP-2） and MMP-9 were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively.

Result

As compared with the blank serum group， the proliferation of MDA-MB-453 cells was promoted and expression of CXCR4 mRNA was increased significantly when SDF-1 was 100 μg·L

-1

（

0.05）. As compared with SDF-1+blank rat serum group， RSR inhibited the proliferation and invasion of MDA-MB-453 cells induced by SDF-1， and at the same time， down-regulated the mRNA and protein expressions of CXCR4， MMP-2 and MMP-9 （

0.05）. After pre-treatment with AMD3100 for 24 h， the inhibitory effect of RSR to cell proliferation was significantly increased （

0.05）， and meanwhile， the decreases in mRNA and protein expression of CXCR4， MMP-2 and MMP-9 were more obvious， with statistically significant differences （

0.05）.

Conclusion

Through SDF-1/CXCR4 biological axis， RSR could down-regulate the expression of MMP-2 and MMP-9， reduce the degradation of extracellular matrix （ECM）， and then inhibit the metastasis of MDA-MB-453 cells. In addition， it has a synergistic effect with CXCR4 inhibitor AMD3100.

关键词

Keywords

references

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