Mechanism of tanshinone IIA to prevent spontaneous breast cancer in mice / 药学学报

To explore the effect of tanshinone IIA (TanIIA) on the occurrence and development of breast cancer, we employed the mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) transgenic mice as a spontaneous breast cancer mouse model. Animal welfare and experimental procedures were in accordance with the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine. The animals were divided into control group, low-dose TanIIA treatment group (30 mg·kg-1·day-1), and high-dose TanIIA treatment group (60 mg·kg-1·day-1). The treatment was administered orally and daily for 5 weeks. The mice were sacrificed after final treatment. Mammary gland and lung were collected for histopathology studies. We evaluated the chemoprophylaxis effect of TanIIA on breast cancer in mice according to the pathological characteristics of breast cancer at different stages of development. Immunofluorescence staining were employed for blood vessel analysis. The expression levels of E-cadherin, proliferating nuclear antigen (PCNA), and oncogene c-Myc were detected by immunohistochemistry. Flow cytometry was used to analyze cell cycle and Cytoscape was used to construct drug-disease protein-protein interaction (PPI) network. Our results showed that TanIIA inhibits breast tumor progression by delaying malignancy from adenoma to early carcinoma, and inhibits blood vessel formation during tumor development. TanIIA (60 mg·kg-1·day-1) inhibits the expression levels of PCNA and c-Myc, upregulates the expression of E-cadherin. In addition, cell cycle experiments showed that the cell cycle of PyMT primary mammary cells in the high-dose TanIIA group was arrested in the G0/G1 phase. Our study demonstrated that TanIIA can significantly inhibit breast tumor progression in MMTV-PyMT mouse model, which may be related to the inhibition of angiogenic switch and cell cycle arrest.

Study on molecular mechanism of circulating tumor cell clusters promoting hematogenous metastasis / 中国药理学通报

Tumor metastasis is an important cause of death in tumor patients. Once metastasis occurs, cancer will become more difficult to treat. Many studies have observed circulating tumor cells (CTCs) in the circulatory system of patients with metastasis. CTCs may occasionally appear in the form of clusters during the process of hematogenous metastasis. These aggregated tumor cell clusters have higher efficacy than the single CTC. The development of circulating tumor cell cluster capture technology provides new insights into tumor metastasis. The molecular mechanism of CTC clusters formation and their role in tumor hematogenous metastasis are discussed here, and their use as biomarkers and target in therapy is evaluated.