摘要:Backgrounds: Cholesterols are the main components of the cell membrane,and play an important role in maintaining normal membrane structure and function. Lovastatin (LOV), the inhibitor of HMG-CoA reductase can lower endogenous cellular cholesterol synthesis, and block the mevalonate (MVA) metabolic pathway. In this paper, we investigate the molecular mechanism of LOV antitumor function through the study of its effect on the membranespotential, cytosolic Ca concentration, gap junctional intercellular communication (GJIC), and the pathways of relatedsignals in MCF-7 mammary cancer cells.Methods: MCF-7 cells were treated for 24-72 h with 4, 8 or 16 μmol/L Lovastatin, and cellular proliferation was examined by MTT assay. Confocal laser microscopy was used to monitor changes in fluorescent marker systems, including the membrane potential-sensitive cation probe diS-C3-(5) and changes in cellular [Ca2+]i. In addition,the expression of plasma membrane calcium ATPase isoform 1 (PMCA1) mRNA was analyzed by RT-PCR, the GJIC function of MCF-7 cells was examined by the scrape-loading and dye transfer (SLDT) technique, and MAPK phosphorylation levels were tested by kinase activity assay.Results: Treatment with 4-16 μmol/L Lovastatin significantly inhibited growth of MCF-7 breast cancer cells. In addition, it increased the negative value of the membrane potential, leading to hyperpolarization of cells. Lovastatin treatment also continuously enhanced [Ca2+]i , although the levels of PMCAI mRNA were unchanged. GJIC was upregulated in MCF-7 cells, with transfer of LY Fluorescence reaching 4-5 rows of cells from the scraped line after treatment with 16 μmnol/L Lovastatin for 72 h. Finally, downregulation of ERK1 and p38MAPK phosphorylation were found in Lovastafin-treated MCF-7 cells.Conclusion: Lovastatin can change intraceUular Ca2+ distributions, increase GJIC function and membrane potential hegativity. This results in hyperpolarization of ceils and changes in the downstream signal cascade that lead to inhibited growth of MCF-7 cells.