Compound C17 inhibits the lung metastasis of breast cancer

doi:10.5246/jcps.2019.10.068

Abstract

Abstract:

Breast cancer is the most common cancer in females with extremely high lethality mainly due to the occurrence of metastasis, which is closely related to cancer stem-like cells (CSCs). It has been reported that CSC frequency in drug-resistant breast cancer and non-small cell lung cancer is reduced by activating dopamine D1 receptor (D1DR). In the present study, we aimed to investigate the effect of a compound C17 that can be used orally for breast cancer metastasis as well as the underlying mechanism involving the activation of D1DR. The confocal immunofluorescence analysis demonstrated that D1DR was up-regulated by C17. The cell survival and colony formation were inhibited by C17 through the detection by Sulforhodamine B colorimetric (SRB) assay and colony formation assay, respectively. Results from both wound healing assay and transwell assay demonstrated that C17 inhibited the migration of 4T1 cells. Flow cytometry analysis indicated that C17 significantly reduced the CSC frequency. In addition, C17 could inhibit the lung metastasis in 4T1 orthotopic mouse model of breast cancer without obvioustoxicity, and it could up-regulate the expression of intratumoral E-cadherin and down-regulate the expressions of Snail and N-cadherin in primary breast tumor, which might be related to the activation of D1DR. Our findings provided a potential candidate compound for the treatment of metastatic breast cancer with good compliance and safety.

Key words: Breast cancer, Metastasis, Cancer stem-like cells, Dopamine D1 receptor, C17

CLC Number:

R962

Supporting:

Yaoyao Feng, Peili Jiao, Xiaoxue Yan, Zixi Xue, Ye Yao, Liang Yang, Daming Kong, Hong Su, Ling Yong, Guoshu Chen, Tianyan Zhou. Compound C17 inhibits the lung metastasis of breast cancer[J]. Journal of Chinese Pharmaceutical Sciences, 2019, 28(10): 716-727.

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