洛伐他汀对BRCA1高表达MCF-7乳腺癌细胞周期调控蛋白的影响

Effects of lovastatin on the cell cycle regulatory proteins in BRCA1-overexpressing MCF-7 cells and the cell proliferation

目的 探讨胆固醇合成抑制剂洛伐他汀 (lovastatin ,LOV)对BRCA1基因高表达MCF 7乳腺癌细胞株细胞周期调控蛋白表达的影响。方法 将BRCA1基因进行扩增、鉴定后 ,运用脂质体转染MCF 7乳腺癌细胞 ,通过MTT比色法检测细胞增殖功能 ,RT PCR方法检测细胞周期调控蛋白cyclinD1、cyclinD3、CDK2、CDK4的mRNA以及Westernblot检测cy clinD1、CDK4蛋白表达水平。结果 LOV处理后 ,细胞的增殖能力减弱 ,cyclinD1、cyclinD3、CDK2、CDK4mRNA表达及cy clinD1、CDK4蛋白表达均降低 ,其中 ,以BRCA1基因高表达MCF 7乳腺癌细胞株经LOV处理后变化更为显著。结论 BR CA1基因在LOV诱导的细胞周期蛋白抑制中可能起重要作用 ,其高表达增强了MCF

Objective To study the effects of lovastatin (LOV) on cyclinD1, cyclinD3, CDK2, and CDK4 in BRCA1 overexpressing MCF 7 cells and the cell proliferation. Methods After amplification and identification of BRCA1 gene, BRCA1 gene was transfected into MCF 7 cells by liposome transfection. The cell proliferation was detected by MTT chromatometry. The mRNA expressions of cyclinD1, cyclinD3, CDK2, and CDK4 and protein expressions of cyclinD1 and CDK4 were analyzed by reverse transcriptase polymerase chain reaction (RT PCR) and Western blotting, respectively. Results LOV weakened the proliferative capacity of cells, and decreased the mRNA expressions of cyclinD1, cyclinD3, CDK2, and CDK4 and the protein expressions of cyclinD1 and CDK4 in cells. These changes were more significant in the transfected cells than that in the nontransfected cells. Conclusion BRCA1 may play a key role in the inhibition of cell cycle regulatory proteins and the cell proliferation induced by LOV. The overexpression of BRCA1 gene may enhance the sensitivity of MCF 7 cells to LOV and the inhibitory effect of LOV on the proliferation of MCF 7 cells.