摘要
目的:观察洛伐他丁对乳腺癌MCF-7细胞膜电位和MAPK活性的影响,探讨其抗癌作用的分子机制。方法:分别用4,8和16μmol/L终浓度的洛伐他丁处理乳腺癌MCF-7细胞24～72h后,采用激光共聚焦显微镜观察膜电位敏感的荧光阳离子分子探针diS-C3-(5)标记的细胞荧光强度的变化,同时分析洛伐他丁对ERK1和P38MAPk蛋白磷酸化水平的影响。结果:4～16μmol/L的洛伐他丁处理细胞后,能明显抑制荧光阳离子分子探针diS-C3-(5)进入胞内,该作用呈一定的剂量效应和时间依赖关系。表明洛伐他丁能明显促使MCF-7细胞膜电位负值加大,诱导细胞发生超极化。此外,实验发现洛伐他丁能显著降低ERK1和P38MAPK蛋白磷酸化水平。结论:洛伐他丁因抑制细胞内源性胆固醇合成、改变膜脂质结构而促进MCF-7细胞膜电位负值增加,诱导细胞发生超极化,同时显著降低MAPK活性。
AIM:To observe the changes of membrane potential and MAPK activity in MCF 7 breast cancer cells treated by Lovastatin,and to explore the anti cancer molecular mechanisms of Lovastatin. METHODS:After treatment for 24-72 hours with 4,8 and 16 μmol/L Lovastatin,the changes of fluorescence intensity of membrane potential sensitive cation molecule probe diS C3 (5) were observed under confocal laser microscope,and the effects of Lovastatin on phosphorylation levels of ERK1 and P38MARK protein were analyzed. RESULTS:4-16 μmol/L Lovastatin treatment could obviously inhibit fluorescence cation molecule probe diS C3 (5) entering into MCF 7 cells in a dose and time dependent manner,which showed that Lovastatin could induce hyperpolarization change through increasing negative value of membrane potential in MCF 7 cells.Meanwhile,a down regulation of the protein phosphorylation levels of ERK1 and P38MAPK was found. CONCLUSION:Lovastatin can increase negative value of membrane potential in MCF 7 cells and lead to hyperpolarization change of cells through blocking the endogenous cholesterol synthesis and change of normal membrane structure, moreover, obviously decrease the activity of MAPK.
出处
《中国临床康复》
CSCD
2004年第8期1490-1491,T005,共3页
Chinese Journal of Clinical Rehabilitation
基金
国家自然科学基金资助项目(30271128)~~
