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.
Low local blood perfusion, high white blood cell and high platelet count are associated with primary tumor growth and lung metastasis in a 4T1 mouse breast cancer metastasis model