洛伐他汀对MCF-7细胞增殖分化功能及间隙连接细胞通讯的影响

Effects of Lovastatin on Proliferation and Gap Junctional IntercellularCommunication of Human Breast Cancer Cell MCF-7

背景与目的:洛伐他汀(lovastatin)是细胞内源性胆固醇合成的抑制剂,临床已普遍用于治疗高脂血症。现有研究报道,洛伐他汀具有抗肿瘤作用,但分子机制尚不清楚。本文探讨洛伐他汀对人乳腺癌细胞MCF-7增殖功能以及间隙连接细胞通讯(gapjunctionalintercellularcommunication,GJIC)的影响。方法:分别以4、8、16μmol/L洛伐他汀处理MCF-7细胞24～72h后,流式细胞仪检测细胞周期的时相分布及细胞凋亡率,硝基蓝四氮唑(NBT)还原实验鉴定细胞分化,并采用划痕标记染料示踪技术观察洛伐他汀对MCF-7细胞GJIC功能的影响。结果:不同浓度洛伐他汀处理细胞不同时间后,MCF-7细胞的增殖明显受抑,抑制率最高可达75.8%,且同一处理时相点各组间比较差异均有显著性(P<0.05);细胞周期分析显示,各处理组内G0/G1期细胞明显增多,处理72h后可高达80%左右;同时洛伐他汀能明显促进MCF-7细胞分化、各处理组间比较差异均有显著性(P<0.01),但洛伐他汀诱导该细胞凋亡的作用不明显。另外,洛伐他汀有上调或恢复MCF-7细胞GJIC的作用;16μmol/L洛伐他汀处理细胞72h后,荧光染料传输的范围可达4～5层细胞。以上作用均有浓度-效应和时间依赖关系。结论:洛伐他汀可抑制MCF-7细胞增殖,使细胞生长阻滞于G0/G1期,并能促进细胞分化,该作用可能与洛伐他?

BACKGROUND &OBJECTIVE:Lovastatin,an inhibitor of endogenous cholesterol biosynthesis,has been widely used in the clinical treatment of hypercholesterolemia.Recently,lovastatin has been paid more attention for its wide range effects on human cancer cells; however,the detail mechanisms of its anti cancer effects are not yet understood. This study was designed to investigate the effects of lovastatin on proliferation and gap junctional intercellular communication (GJIC) of MCF 7 human breast cancer cells. METHODS:After treated with lovastatin at dosages of 4,8,16 μmol/L for 1-3 days,the cell differentiation was examined with nitroblue tetrazolium (NBT) reduction test;the proliferation and distribution of cell cycles were examined with flow cytometry (FCM). Meanwhile,GJIC of MCF 7 cells was observed using the scrape loading and dye transfer(SLDT) technique. RESULTS:Lovastatin could inhibit the proliferation of MCF 7 cells significantly and 75.80 percent of cells were inhibited after treated with 16 μmol/L lovastatin for 72 hours (P< 0.05). Meanwhile, lovastatin could arrest MCF 7 cells in the G0/G1 phase of cell cycle and 80 percent of cells were arrested in G0/G1 phase after treated with lovastatin for 72 hours. Furthermore, lovastatin could induce the differentiation of MCF 7 cells (P< 0.01) and up regulate GJIC in MCF 7 cells. After treated with 16 μmol/L lovastatin for 72 hours, transfer of LY fluorescence could reach 4-5 rows of cells from the scraped line. However, apoptosis in MCF 7 cells was not obvious. All these effects of lovastatin were in a dose and time dependent manner. CONCLUSION:It suggests that lovastatin has the capabilities of inhibiting proliferation, arresting MCF 7 cells at G0/G1 phase of cell cycle and inducing differentiation. These effects of lovastatin maybe correlate with lovastatin promoting GJIC function in MCF 7 cells.