Department of Traditional Chinese Medicine Oncology, Provincial Hospital of Anhui Medical University, Hefei 230001, China.
Chin J Integr Med. 2012 Aug;18(8):605-9. doi: 10.1007/s11655-012-1184-x. Epub 2012 Aug 2.
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.
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.
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).
Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.
研究马钱子碱对乳腺癌裸鼠骨转移模型血管内皮生长因子（VEGF）表达和微血管密度（MVD）的影响，探讨马钱子碱的抗肿瘤作用机制。
采用注射器针头直接向右侧后腿骨股皮质内注射 0.2 mL 单倍体悬液（含 2×10(5)个人乳腺癌细胞）建立模型。25 只裸鼠随机分为 5 组，连续 8 天腹腔注射生理盐水或药物：模型组（0.2 mL 生理盐水）、低剂量马钱子碱组（1.73 mg·kg(-1)）、中剂量马钱子碱组（3.45 mg·kg(-1)）、高剂量马钱子碱组（6.90 mg·kg(-1)）和反应停组（200 mg·kg(-1)）。记录饮食和活动情况，5 周后收获肿瘤。采用苏木精-伊红染色和免疫组织化学染色检测 VEGF 阳性细胞的百分比，光学显微镜检测 MVD 表达。
与模型组相比，马钱子碱或反应停处理组的 VEGF 表达明显降低（P <0.01）。高剂量马钱子碱组与反应停组之间无显著差异（P >0.05）。高剂量马钱子碱组与低剂量马钱子碱组之间存在显著差异（P<0.05）。此外，与反应停组相比，低剂量和中剂量马钱子碱组的 VEGF 表达明显增加（P <0.05）。3 个马钱子碱组和反应停组的 MVD 值均明显低于模型组（P <0.01）。中、高剂量马钱子碱组与反应停组的 MVD 值无显著差异（P >0.05），而低剂量组的 MVD 值与反应停组相比显著增加（P <0.05）。
马钱子碱可抑制乳腺癌骨转移的生长，可能通过抑制肿瘤血管生成。
