Synergic effect of eicosapentaenoic acid and lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells.
Synergic effect of eicosapentaenoic acid and lovastatin on gene expression of HMGCoA reductase and LDL receptor in cultured HepG2 cells.
复制标题
DOI：
10.1186/1476-511x-9-135
复制
发表时间：
2010-11-30
影响因子：
4.5
通讯作者：
Caruso MG
中科院分区：
文献类型：
--
作者：
Notarnicola M;Messa C;Refolo MG;Tutino V;Miccolis A;Caruso MG
多不饱和脂肪酸是3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶的有效抑制剂，HMG-CoA是一种催化HMGCoA转化为甲羟戊酸的酶，甲戊酸是胆固醇生物合成的限速步骤。他汀类药物是一类被广泛用于治疗高胆固醇血症的药物，因为它们能够抑制胆固醇的生物合成，并上调肝脏低密度脂蛋白(LDL)受体的合成。多不饱和脂肪酸介导了他汀类药物的许多(如果不是全部)作用，这可能是它们降低胆固醇水平的一个机制。本研究旨在探讨二十碳五烯酸(EPA)联合洛伐他汀对人肝癌细胞株HMGCoA还原酶和低密度脂蛋白受体基因表达的调节作用。联合应用EPA和洛伐他汀可增强对HMGCoA还原酶和低密度脂蛋白受体基因表达的调节作用。此外，我们还检测到EPA和洛伐他汀联合应用对抑制癌细胞增殖有协同作用。EPA联合小剂量洛伐他汀治疗肿瘤可能具有潜在的应用价值。
PUFAs are potent inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, an enzyme catalyzing the conversion of HMGCoA to mevalonate, the rate limiting step in cholesterol biosynthesis. Statins represent a class of drugs that are widely used to treat hypercholesterolemia for their ability to inhibit cholesterol biosynthesis and to up-regulate the synthesis of Low Density Lipoprotein (LDL) receptors in the liver. PUFAs mediate many, if not all, actions of statins and this could be one mechanism by which they lower cholesterol levels. The purpose of this study was to investigate whether combined treatment with Eicosapentaenoic acid (EPA) and lovastatin enhanced the regulatory effect on gene expression of HMGCoA reductase and LDL receptor in HepG2 cell line. The combined treatment with EPA and lovastatin enhanced the regulatory effect on gene expression of HMGCoA reductase and LDL receptor in HepG2 cell line. Moreover, we detected a synergistic effect on the inhibition of cancer cell proliferation obtained by combination of EPA and Lovastatin. The use of EPA, in combination with low doses of Lovastatin may have potential value in treatment of neoplastic diseases.