Realgar Nanoparticles Inhibit Migration, Invasion and Metastasis in a Mouse Model of Breast Cancer by Suppressing Matrix Metalloproteinases and Angiogenesis.

Abstract:

BACKGROUND:Realgar, a traditional Chinese medicine, has shown antitumor efficacy in several tumor types. We previously showed that realgar nanoparticles (nano-realgar) had significant antileukemia, anti-lung cancer and anti-liver cancer effects. In addition, the anti-tumor effects of nanorealgar were significantly better than those of ordinary realgar. OBJECTIVE:To explore the inhibitory effects and molecular mechanisms of nano-realgar on the migration, invasion and metastasis of mouse breast cancer cells. METHODS:Wound-healing migration assays and Transwell invasion assays were carried out to determine the effects of nano-realgar on breast cancer cell (4T1) migration and invasion. The expression levels of matrix metalloproteinase (MMP)-2 and -9 were measured by Western blot. A murine breast cancer metastasis model was established, administered nano-realgar for 32 days and monitored for tumor growth and metastasis by an in vivo optical imaging system. Finally, living imaging and hematoxylin and eosin (HE) staining were used to measure the morphology and pathology of lung and liver cancer cell metastases, respectively. Angiogenesis was assessed by CD34 immunohistochemistry. RESULTS:Nano-realgar significantly inhibited the migration and invasion of breast cancer 4T1 cells and the expression of MMP-2 and -9. Meanwhile, nano-realgar effectively suppressed the abilities of tumor growth, metastasis and angiogenesis in the murine breast cancer metastasis model in a time- and dosedependent manner. CONCLUSION:Nano-realgar significantly inhibited migration and invasion of mouse breast cancer cells in vitro as well as pulmonary and hepatic metastasis in vivo, which may be closely correlated with the downexpression of MMP-2 and -9 and suppression of tumor neovascularization.

journal_name

Curr Drug Deliv

journal_title

Current drug delivery

authors

Xiaoxia X,Jing S,Dongbin X,Yonggang T,Jingke Z,Yanying Z,Hulai W

doi

10.2174/1567201817666200115105633

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

148-158

issue

2

eissn

1567-2018

issn

1875-5704

pii

CDD-EPUB-103658

journal_volume

17

pub_type

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