Hirudin Suppresses Metastasis of Human Breast Adenocarcinoma Cells In Vitro and in a Zebrafish Xenograft Model

Abstract

Background: Breast cancer is the leading cause of cancer-related death in women worldwide. Hirudin has been shown to inhibit the growth and metastasis of several types of cancers in experimental tumor models. However, whether hirudin exerts antitumor effects on breast adenocarcinoma cells has not yet been investigated. The objective of this study was to evaluate the antitumor effects and explore the underlying mechanisms of hirudin in breast adenocarcinoma MCF-7 cells. Methods: The viability of MCF-7 cells was assayed by Cell Counting Kit-8. The adhesion ability of the cells was evaluated by cell adhesion assay. Besides, cell migration was detected by wound healing assay. Cell invasion was examined using Transwell chamber assay. The underlying molecular mechanism was investigated by immunofluorescence. In addition, In vivo zebrafish xenograft model was used to verify the proliferation and metastasis of hirudin on MCF-7 cells. Results: The results showed that hirudin significantly inhibited the cell viability and suppressed cell adhesion, migration, invasion compared with the control group. Importantly, hirudin significantly decreased the expression of CHD1L, MDM2 protein, and increased the expression of p53 protein. Moreover, the zebrafish xenograft study revealed that hirudin inhibited the proliferation and metastasis of MCF-7 cells in vivo. Conclusion: The present findings demonstrate that hirudin suppressed metastasis of MCF-7 cells and the mechanism may involve with the CHD1L/MDM2/p53 axis. Hirudin is a promising antineoplastic agent for the treatment of breast cancer with significant antimetastatic activities. Keywords: Breast cancer, Hirudin, Metastasis, Zebrafish, CHD1L