关键词: 辛伐他汀, 缝隙连接, 肝癌

Abstract:

Background and purpose: It has been reported that gap junctional (GJ) function was significantly decreased in hepatocellular carcinoma (HCC) tissues and cell lines. However, the increased GJ suppress tumorigenesis and the development of liver cancer. This study therefore aimed to examine the effect of simvastatin on GJ function between Hep3b cells. Thus, the exploition of drugs to increase GJ function between liver cancer cells will provide an efficient approach to fight against liver tumor as well as increase cytotoxicity of antitumor agents. Methods: SRB was used to assay the toxicity of simvastatin. The effect of simvastatin on GJ function was determined by “Parachute” dye-coupling assay and scrape loading/dye transfer assay. Results: Pretreated Hep3b cells with simvastatin at the concentration of 1, 5 or 10 μmol/L for 24 h did not induce the cytotoxicity. So simvastatin at the concentration of 5 and 10 μmol/L would not reduce the amount of GJ on cell membranes. “Parachute” dye-coupling assay showed that the treatment with 5 and 10 μmol/L simvastatin for 4 h enhanced the dye spread through GJ in Hep3b cells. Similarly, scrape loading/dye transfer assay showed that simvastatin could induce the increasing spread of lucifer yellow (Ly,Sigma) around the scofing cells with increasing concentrations. Conclusion: Simvastatin could increase the GJ function of Hep3b cells.

Key words: Simvastatin, Gap junction, Hepatoma carcinoma