Effects of brucine on vascular endothelial growth factor expression and microvessel density in a nude mouse model of bone metastasis due to breast cancer.

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 2×10(5) 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.

• Authors: Ping Li, Mei Zhang, Wen-Jing Ma, Xin Sun, Fu-Peng Jin
• Journal: Chinese journal of integrative medicine (Chin J Integr Med) Vol. 18 Issue 8 Pg. 605-9 (Aug 2012) ISSN: 1672-0415 [Print] China
• PMID: 22855035 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vascular Endothelial Growth Factor A
• brucine
• Strychnine

Topics

• Animals
• Bone Neoplasms (blood supply, metabolism, secondary)
• Breast Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Disease Models, Animal
• Female
• Humans
• Immunohistochemistry
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Microvessels (drug effects, pathology)
• Strychnine (analogs & derivatives, pharmacology, therapeutic use)
• Vascular Endothelial Growth Factor A (metabolism)
• Xenograft Model Antitumor Assays