Mechanism of tanshinone IIA to prevent spontaneous breast cancer in mice
10.16438/j.0513-4870.2021-1468
- VernacularTitle:丹参酮IIA预防小鼠自发性乳腺癌发生的作用机制
- Author:
Yuan WANG
1
;
Xiao-feng LI
2
,
3
;
Ye SUN
1
;
Jun-de XU
1
;
Yi-chuang WU
1
;
Peng WAN
1
;
Rui DENG
1
;
Xiu-qin ZHENG
1
;
Xiao-man LI
1
;
Yang ZHAO
2
,
3
;
Yin LU
1
,
4
;
Yuan-yuan WU
1
Author Information
1. Jiangsu Key Laboratory for Pharmacology and Safety Evaluation of Chinese Materia Medica, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China
2. School of Medicine &
3. Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China
4. Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing 210023, China
- Publication Type:Research Article
- Keywords:
tanshinone IIA;
italic>Salvia miltiorrhiza;
breast neoplasm;
chemoprevention;
carcinogenesis
- From:
Acta Pharmaceutica Sinica
2021;56(12):3277-3284
- CountryChina
- Language:Chinese
-
Abstract:
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.
