ABSTRACT
AIM:To investigate the effect of hirsutine on hypoxia-induced migration and invasion abilities of human breast cancer MCF-7 cells and its possible mechanism. METHODS:CCK-8 assay was employed to detect the cyto-toxic effect of hirsutine on the MCF-7 cells. Cell migration was observed by wound healing assay,and cell invasion ability was measured by Transwell invasion assay. Western blot was used to analyze the protein levels of hypoxia-inducible factor-1α(HIF-1α),Snail,E-cadherin and matrix metalloproteinase-9 (MMP-9). The mRNA levels of HIF-1α was detected by RT-PCR. RESULTS:Hirsutine remarkably reduced the cell viability from 32 μmol/L(P<0.05),and the IC50value was 62.82 μmol/L. In hypoxia state,MCF-7 cells showed more powerful capabilities of migration and invasion (P<0.05), higher protein levels of HIF-1α,Snail and MMP-9 (P<0.05),lower protein level of E-cadherin(P<0.05),and higher mRNA level of HIF-1α (P<0.05). These hypoxia-induced effects were all inhibited by hirsutine at 16 μmol/L (P<0.05),apart from the mRNA level of HIF-1α. CONCLUSION:Hirsutine inhibits hypoxia-induced migration and inva-sion in human breast cancer MCF-7 cells most likely via down-regulation of the protein levels of HIF-1α,Snail and MMP-9,and up-regulation of the protein level of E-cadherin.