PROMEC Unit, Medical Research Council, P.O. Box 19070, Tygerberg 7505, South Africa.
Prostaglandins Leukot Essent Fatty Acids. 2009 Nov-Dec;81(5-6):391-9. doi: 10.1016/j.plefa.2009.08.003. Epub 2009 Sep 25.
Altered membrane integrity in hepatocellular carcinoma (HCC) tissue was indicated by an elevation in cholesterol and significant decrease in phosphatidylcholine (PC). The resultant decreased phosphatidylcholine/phosphatidylethanolamine (PC/PE) and increased cholesterol/phospholipid ratios are associated with decreased fluidity in the carcinoma tissue. The lower PC was associated with a decrease in the quantitative levels of the saturated (C16:0, C18:0), omega6 (C18:2, C20:4) and omega3 (C22:5, C22:6) fatty acids (FAs), resulting in reduced long-chain polyunsaturated fatty acids (LCPUFAs), total PUFA and an increase in omega6/omega3 FA ratio. In PE, the saturated and omega3 (C22:5, C22:6) FAs were reduced while the total omega6 FA level was not affected, leading to an increased omega6/omega3 FA ratio. Increased levels of C18:1omega9, C20:2omega6 and reduction of 22:6omega3 in PC and PE suggest a dysfunctional delta-6 desaturase. The reduced PC/PE ratio resulted in a decreased C20:4omega6 (PC/PE) ratio, implying a shift towards synthesis of the 2-series eicosanoids. Lipid peroxidation was reduced in both hepatitis B negative (HBV(-)) and positive (HBV(+)) HCC tissues. Glutathione (GSH) was decreased in HCC while HBV had no effect, suggesting an impairment of the GSH redox cycle. In contrast HBV infection enhanced GSH in the surrounding tissue possibly to counter oxidative stress as indicated by the increased level of conjugated dienes. Apart from the reduced LCPUFA, the low level of lipid peroxidation in the carcinoma tissue was associated with increased superoxide dismutase and glutathione peroxidase activity. The disruption of the redox balance, resulting in increased cellular antioxidant capacity, could create an environment for resistance to oxidative stress in the carcinoma tissue. Alterations in membrane cholesterol, phospholipids, FA parameters, C20:4omega6 membrane distribution and low lipid peroxidation are likely to be important determinants underlying the selective growth advantage of HCC cells.
肝癌（HCC）组织中胆固醇升高和磷脂酰胆碱（PC）显著减少表明细胞膜完整性发生改变。由此导致的 PC/磷脂酰乙醇胺（PC/PE）比值降低和胆固醇/磷脂比值升高与癌组织流动性降低有关。较低的 PC 与饱和脂肪酸（C16:0、C18:0）、ω6（C18:2、C20:4）和 ω3（C22:5、C22:6）脂肪酸（FA）的定量水平降低有关，导致长链多不饱和脂肪酸（LCPUFA）、总 PUFA 减少和 ω6/ω3 FA 比值升高。在 PE 中，饱和和 ω3（C22:5、C22:6）FA 减少，而总 ω6 FA 水平不受影响，导致 ω6/ω3 FA 比值增加。PC 和 PE 中 C18:1ω9、C20:2ω6 的水平升高和 22:6ω3 的减少表明 δ-6 去饱和酶功能障碍。PC/PE 比值降低导致 C20:4ω6（PC/PE）比值降低，表明向 2 系列类二十烷酸合成的转变。乙型肝炎阴性（HBV(-)) 和阳性（HBV(+)) HCC 组织中的脂质过氧化均减少。GSH 在 HCC 中减少，而 HBV 没有影响，表明 GSH 氧化还原循环受损。相反，HBV 感染增强了周围组织中的 GSH，可能是为了对抗氧化应激，正如共轭二烯水平的增加所表明的那样。除了 LCPUFA 减少外，癌组织中低水平的脂质过氧化与超氧化物歧化酶和谷胱甘肽过氧化物酶活性增加有关。氧化还原平衡的破坏导致细胞抗氧化能力增加，可能为 HCC 细胞对氧化应激的抵抗创造了环境。膜胆固醇、磷脂、FA 参数、C20:4ω6 膜分布和低脂质过氧化的改变可能是 HCC 细胞选择性生长优势的重要决定因素。
