ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>Brucine could inhibit the growth of breast cancer to bone metastases, possibly by inhibiting tumor angiogenesis.</p>
Subject(s)
Animals , Female , Humans , Mice , Bone Neoplasms , Metabolism , Breast Neoplasms , Metabolism , Pathology , Cell Line, Tumor , Disease Models, Animal , Immunohistochemistry , Mice, Inbred BALB C , Mice, Nude , Microvessels , Pathology , Strychnine , Pharmacology , Therapeutic Uses , Vascular Endothelial Growth Factor A , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
Cell apoptosis is an initiative process of cell death regulated by genes. Inducing cell apoptosis is a new way of cancer treatment. In this paper, the progress in experimental studies on the effect of Chinese herbal compounds (CHC) on the induction of tumor cell apoptosis will be reviewed in terms of major mechanisms (gene expression regulation, cell morphology change, telomerase activity change, and immunity enhancement, etc.). The study on disassembled CHC, as well as the synergistic effect when in combined use with chemotherapy for inducing apoptosis, is also reviewed here.