Tetramethylpyrazine inhibits hypoxia-induced migration and invasion of breast cancer cell line MDA-MB-435S in vitro

Objective: To investigate the effect of tetramethylpyrazine (TMP), a major active component in Chinese medicine Ligusticum chuanxiong, on metastasis of breast cancer cell line MDA-MB-435S in vitro, and its possible mechanism.Methods: MDA-MB-435S cells were cultured under hypoxic condition, which could trigger malignant metastatic potential of tumor cells in vitro. Thus, the concentration of TMP which could not affect the proliferaion of hypoxic MDA-MB-435S cells was determined by MTT assay. The morphology of MDA-MB-435S cells treated with TMP under hypoxic condition was observed by immunofluorescence. The capacities of invasion and migration of hypoxic MDA-MB-435S cells were determined by Transwell chamber and Wound healing assays, respectively. The expressions of hypoxia-inducible factor-1α (HIF-1α)-mediated metastasis-related proteins, such as vascular endothelial growth factor-A (VEGF-A), lysyl oxidase-1 (LOX-1), Snail and Slug, were detected by Western blotting.Results: TMP could significantly change the morphology and inhibit the metastasis of MDA-MB-435S cells cultured under hypoxic condition, improve the morphology of the cells, reduce the number of stress fibers of F-actin, and inhibit the capacities of invasion and migration of the cells in vitro. Moreover, TMP reduced the expression levels of HIF-1α–mediated metastasis-related target proteins VEGF-A, LOX-1, Snail and Slug proteins through decreasing the expression of HIF-1α under hypoxic condition, which resulted in the inhibition of metastasis of MDA-MB-435S cells.Conclusion: These findings indicate that TMP can inhibit the metastasis of breast cancer MDA-MB-435S cells by reducing the expressions of HIF-1α and the metastasis-related target proteins in vitro. Therefore, TMP may be an effective agent to prevent hypoxia-induced metastasis of breast cancer. DOI:10.3781/j.issn.1000-7431.2015.11.147