Effect of Extracts from Veronica peregrine on Breast Cancer Cell-induced Osteoclastic Bone Metastasis via Inhibiting Runx2 Activation
10.13422/j.cnki.syfjx.20220624
- VernacularTitle:蚊母草提取物通过抑制Runx2活性抗乳腺癌破骨性骨转移作用
- Author:
Sheng-ling LIU
1
;
Hong LYU
1
;
Hui-ru TIAN
1
;
Si-qin JIANG
1
;
Ping YUAN
1
;
Wei-ran FU
2
;
Shu-liang GAO
1
;
Jian-jiang FU
1
Author Information
1. Jiangxi University of Chinese Medicine， Nanchang 330004， China
2. School of Basic Medical Sciences， Capital Medical University， Beijing 100069， China
- Publication Type:Journal Article
- Keywords:
Veronica peregrina;
osteoclastic bone metastasis;
breast cancer;
Runt-related transcription factor 2 （ Runx2 ）;
receptor activator of nuclear factor-κB （RANK）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2022;28(7):81-87
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate inhibitory effect of extracts from Veronica peregrina （EVP） on the osteoclastic bone metastasis induced by breast cancer cells. MethodBone metastasis model was established by injection of MDA-MB-231 cells， a human breast cancer cell line， into the left ventricle of BALB/c nude mice. The expression of human cytokeratin-19 （Ck-19） gene in mouse bone marrow was determined by nested polymerase chain reaction（PCR） to assess the bone metastasis of MDA-MB-231 cells. To assess the effects of EVP on the activation of bone marrow macrophages （BMMs）， we counted the multinuclear cells and measured the secretion of Cathepsin K. Western blot was adopted to assess the effects of EVP on receptor activator of nuclear factor-κB （RANK）， Runt-related transcription factor 2 （ Runx2 ）， phosphorylated Runx2 （p-Runx2）， and matrix metalloproteinase-9 （MMP-9） in BMMs. Gelatin zymography was employed to determine the activities of matrix metalloproteinases （MMPs）. ResultCompared with that in the blank group， Ck-19 expression was down-regulated in EVP groups （P<0.05）. The multinucleated cells increased when the BMMs were induced by soluble receptor activator of nuclear factor-κB ligand （sRANKL）， which was inhibited by EVP （P<0.05）. The level of cathepsin K in the supernatant of sRANKL group increased compared with that of the blank group， while EVP groups had lower cathepsin K levels than sRANKL group （P<0.05）. Compared with the blank group， the sRANKL group showed up-regulated RANK expression， Runx2 phosphorylation， and MMP-9 expression （P<0.05）， while the expression levels of RANK， p-Runx2， and MMP-9 were down-regulated when the cells were incubated with EVP （P<0.05）. Furthermore， exposure of BMMs to sRANKL resulted in an increase in gelatin hydrolyzation compared with the blank group （P<0.01）， which， however， was reversed in EVP groups （P<0.05）. ConclusionEVP significantly inhibits bone marrow metastasis of MDA-MB-231 cells， which may be associated with the suppression of osteoclast activation by inhibiting Runx2 phosphorylation.
