Laboratory of Biochemistry, National Institute for Digestive Diseases Castellana Grotte, Bari, Italy.
Lipids Health Dis. 2010 Nov 30;9:135. doi: 10.1186/1476-511X-9-135.
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.
多不饱和脂肪酸（PUFAs）是强效的 3-羟基-3-甲基戊二酰辅酶 A（HMG-CoA）还原酶抑制剂，该酶催化 HMGCoA 转化为甲羟戊酸，这是胆固醇生物合成的限速步骤。他汀类药物是一类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生物合成，并上调肝脏中低密度脂蛋白（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种机制。本研究旨在探讨二十碳五烯酸（EPA）和洛伐他汀联合治疗是否增强了对 HepG2 细胞系中 HMGCoA 还原酶和 LDL 受体基因表达的调节作用。
EPA 和洛伐他汀联合治疗增强了对 HepG2 细胞系中 HMGCoA 还原酶和 LDL 受体基因表达的调节作用。此外，我们还检测到 EPA 和洛伐他汀联合使用对抑制癌细胞增殖的协同作用。
联合使用 EPA 和低剂量洛伐他汀可能在治疗肿瘤疾病方面具有潜在价值。
