辛伐他汀对肝癌细胞间缝隙连接功能的影响研究  

The effect of simvastatin on the gap junction function of hepatocellular carcinoma cells

作　　者：汪灵芝[1] 彭建新[2] 余美玲[3] 黄焕森[1] 

机构地区：[1]广州医科大学附属第二医院麻醉科,广东广州510260 [2]广东省中医院肝胆外科,广东广州510120 [3]安徽省蚌埠医学院附属第一医院药剂科,安徽蚌埠233004

出　　处：《中国癌症杂志》2014年第9期641-645,共5页China Oncology

基　　金：广州市博士启动项目(No:2011c49);广州市医药卫生科技项目(No:20141A011083)

摘　　要：背景与目的:肝癌的发生、发展过程中伴随着细胞间缝隙连接(gap junction,GJ)功能的下降,恢复或增强肿瘤细胞间的GJ可以抑制肿瘤细胞的恶性转化和生长增殖。本研究拟通过观察辛伐他汀对肝癌细胞间GJ功能的影响,寻找能够增强GJ功能的药物,从而为肝癌的治疗提供新策略和新手段。方法:采用磺酰罗丹明B法观察辛伐他汀对大鼠肝癌细胞Hep3b的抑制作用;细胞接种荧光法和划痕标记/染料示踪技术观察辛伐他汀对GJ功能的影响。结果:1、5和10μmol/L辛伐他汀在24 h作用时间内均对细胞生长无抑制作用,将不影响GJ的数量;取5、10μmol/L辛伐他汀作用细胞4 h后,与对照组相比,GJ的荧光传递功能明显增强;与对照组相比,5、10μmol/L辛伐他汀作用细胞4 h后,荧光黄染料(lucifer yellow,Ly,Sigma)传输范围随着辛伐他汀浓度的升高逐渐增大。结论:辛伐他汀可以增强肝癌细胞GJ功能。Background and purpose：It has been reported that gap junctional （GJ） function was signiifcantly 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 efifcient approach to ifght 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 scoifng cells with increasing concentrations.Conclusion：Simvastatin could increase the GJ function of Hep3b cells.

关 键 词：辛伐他汀 缝隙连接 肝癌 

分 类 号：R735.7[医药卫生—肿瘤]