Breast cancer (BC) is the most frequently malignancy in women. Therefore, establishment of an animal model for the development of preventative measures and effective treatment for tumors is required. A novel heterogeneous spontaneous mammary tumor animal model of Kunming mice was generated. The purpose of this study was to characterize the spontaneous mammary tumor model. Histopathologically, invasive nodular masses of pleomorphic tubular neoplastic epithelial cells invaded fibro-vascular stroma, adjacent dermis and muscle tissue. Metastatic spread through blood vessel into liver and lungs was observed by hematoxylin eosin staining. No estrogen receptor (ER) or progesterone receptor (PR) immunoreactivity was detected in their associated malignant tumors, human epidermal growth factor receptor-2 (HER-2) protein weak expression was found by immunohistochemistry. High expression of vascular endothelial growth factor (VEGF), moderate or high expression of c-Myc and cyclin D1 were observed in tumor sections at different stages (2, 4, 6 and 8 weeks after cancer being found) when compared with that of the normal mammary glands. The result showed that the model is of an invasive ductal carcinoma. Remarkably in the mouse model, ER and PR-negative and HER2 weak positivity are observed. The high or moderate expressions of breast cancer markers (VEGF, c-Myc and cyclin D1) in mammary cancer tissue change at different stages. To our knowledge, this is the first report of a spontaneous mammary model displaying colony-strain, outbred mice. This model will be an attractive tool to understand the biology of anti-hormonal breast cancer in women.
Natural pigments are known for possessing a wide range of pharmacological and health-promoting properties. The pigments, produced by a new strain Fusarium (Fusarium sp. JN158) previously identified in our laboratory, were found to have 6 peaks (representing 6 compounds) by high-performance liquid chromatography with a diode-array detector (HPLC-DAD) separation. The 6th peak compound (compound VI) is a benzoquinone compound. In this study, we examined the effects of compound VI on the proliferation of breast cancer cells and aimed to elucidate the underlying mechamisms. Compound VI exerted anti-proliferative effects on MCF-7 estrogen receptor (ER)+ cells in a dose-dependent manner (IC25, 7 µM; IC50, 11 µM), whereas it had no effect on MDA-MB-231 ER− cells and normal cells. The cell index (CI) began to decrease at 24 h following treatment with benzoquinone. Mechanistically, the results from molecular analysis revealed that compound VI inhibited the expression of ERα, progesterone receptor (PR), vascular endothelial growth factor (VEGF), Bcl-2, cyclin D1 and nuclear factor-κB (NF-κB) p65, while it increased the expression of cleaved caspase-3 and Bax in the MCF-7 cells. Taken together, our findings indicate that compound VI exerts anti-proliferative effects on MCF-7 cells through the NF-κB pathway via the regulation of ER signaling. Our data may indicate that benzoquinone from Fusarium pigment may have potential for use as an anti-proliferative agent in the treatment of breast cancer.
Background Boschniakia rossica (Cham. & Schltdl.) B. Fedtsch. (Bu-Lao-Cao in Chinese name) is a famous Chinese traditional drug and mainly distributed in Korea, Japan, Russia, and China. The dried whole grass of Boschniakia rossica is commonly used in traditional Chinese medicine to treat kidney deficiency, yang deficiency, waist and knee aches and constipation. In order to quantify the active ingredients in B. rossica chinensis and body weight, clinical features and serum SOD and MDA activities, cAMP, cGMP, and testosterone (T), follicle-stimulating growth hormone (FSH), mouse bone morphogenetic protein-5 (BMP-5), mouse activin receptor IIA (ActRIIA) were measured to elucidate the mechanism underlying its treatment of kidney yang deficiency potential. Methods Extracts of B. rossica were evaluated by HPLC-MS analyses. Kidney-yang deficiency syndrome was induced in mouse with hydrocortisone (10 mg/Kg, 15d) and treated with B. rossica extract. The animals were treated orally with 3 doses of B. rossica extract: 1000, 500 and 250 mg/Kg, for 15 days. Body weight and clinical characteristics were recorded daily. For biochemical analyses, the following tests were performed: superoxide dismutase (SOD) activity, malondialdehyde (MDA) activity, testosterone (T) content, follicle growth hormone (FSH) content, cyclic adenosine monophosphate (cAMP) content, mouse bone morphogenetic protein-5 (BMP-5) content and activin receptor IIA (ActRIIA) content. Results Our study found that all the mice except the blank group showed significant systemic depletion caused by hydrocortisone. Low T content, low cAMP activity and high cGMP content were consistent with the physiological and biochemical indexes of kidney-yang deficiency syndrome. After oral gavage, the pathological conditions were improved in both the Positive group and the B. rossica groups.Conclusions The high-dose extract of B. rossica showed similar therapeutic effects as Jingui Shenqi Pill. The extract of B. rossica can be used to treat with hydrocortisone-induced kidney yang deficiency syndrome by increasing serum testosterone content and decreasing FSH content. More importantly, the experiment found that activin A and BMP-5 also have effects on kidney yang deficiency syndrome.
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