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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 7乳腺癌细胞对LOV的敏感性和LOV对乳腺癌细胞的增殖抑制作用
Objective To investigate the effect of cholesterol synthesis inhibitor lovastatin (LOV) on the expression of cell cycle regulatory proteins of breast cancer cell line MCF-7 with high expression of BRCA1 gene. Methods The BRCA1 gene was amplified and identified. After being transfected into MCF7 breast cancer cells by lipofectamine 2000, the proliferation of breast cancer cells was detected by MTT colorimetric assay. The mRNA expressions of cyclinD1, cyclinD3, CDK2 and CDK4 Western blot was used to detect the expression of cy clinD1 and CDK4 protein. Results After LOV treatment, the proliferation of cells was weakened and the expressions of cyclinD1, cyclinD3, CDK2 and CDK4 mRNA and the expression of cy clinD1 and CDK4 proteins were decreased. The changes of MCF-7 breast cancer cell lines with BRCA1 gene expression were more obvious after LOV treatment . Conclusion The BR CA1 gene may play an important role in LOV-induced inhibition of cyclin. The high expression of BR CA1 enhances the sensitivity to LOV in MCF 7 breast cancer cells and the inhibitory effect of LOV on the proliferation of breast cancer cells