Abstract
Objective
To study the effects of brucine on vascular endothelial growth factor (VEGF) expression and microvessel density (MVD) in a nude mouse model of bone metastasis due to breast cancer, and to assess the possible antitumor mechanism of brucine.
Methods
A syringe needle was used to directly inject 0.2 mL monoplast suspension (with 2×105 human breast cancer cells contained) into the bony femoral cortex of the right hind leg for modeling. Twenty-five nude mice were randomized into five groups and administered with an intraperitoneal injection of saline or drug for 8 consecutive days: model group (0.2 mL normal saline), low-dose brucine group (1.73 mg·kg−1), medium-dose brucine group (3.45 mg·kg−1), high-dose brucine group (6.90 mg·kg−1), and thalidomide group (200 mg·kg−1). Diet and activity were recorded, and the tumors were harvested 5 weeks later. The percentage of VEGF-positive cells was determined with hematoxylin and eosin staining and immunohistochemical staining, and MVD expression was determined by optical microscopy.
Results
The VEGF expressions in brucine- or thalidomide-treated mice were significantly reduced as compared with mice in the model group (P <0.01). There were no significant difference between the high-dose brucine group and the thalidomide group (P >0.05). Significant difference was between the high- and low-dose brucine group P<0.05). Further, VEGF expression was significantly increased in the low- and medium-dose brucine groups compared with the thalidomide group (P <0.05). The MVD values in the three brucine and thalidomide groups were significantly lower than that in the model group (P <0.01). The MVD values in the medium- and high-dose brucine groups were not significantly different from those in the thalidomide group (P >0.05), while the MVD value showed a significant increase in the low-dose group compared with the thalidomide group (P <0.05).
Conclusion
Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.
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Supported by the State Administration of Traditional Chinese Medicine of China (2009-No.30)
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Li, P., Zhang, M., Ma, Wj. et al. Effects of brucine on vascular endothelial growth factor expression and microvessel density in a nude mouse model of bone metastasis due to breast cancer. Chin. J. Integr. Med. 18, 605–609 (2012). https://doi.org/10.1007/s11655-012-1184-x
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DOI: https://doi.org/10.1007/s11655-012-1184-x