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我们以前曾报道花生四烯酸(arachidonic acid,AA)代谢产物可以促进乳腺癌细胞增殖和迁移.为了进一步寻找维持高转移乳腺癌细胞中AA高水平代谢的内源机制,深入探求AA代谢促进乳腺癌细胞转移的分子机理,我们应用HPLC/ESI/MSn技术检测和分析了乳腺癌MCF-7和高转移乳腺癌LM-MCF-7细胞中溶血磷脂酰胆碱(lysophosphatidylcholines,Lyso PCs)和磷脂酰胆碱(phosphatidylcholines,PCs)的成分和含量.发现了10种Lyso PC的含量在LM-MCF-7细胞中显著高于MCF-7细胞,有6种PC可水解产生AA,它们在LM-MCF-7细胞中的含量显著低于MCF-7细胞,提示这些溶血磷脂含量的升高和磷脂含量的降低可能与乳腺癌转移相关.在LM-MCF-7细胞中,COX-2抑制剂吲哚美辛(indomethacin,Indo)和LOX抑制剂(nordihydroguaiaretic acid,NDGA)共同作用可明显下调c PLA2的活性,应用HPLC-ESI-MSn技术比较c PLA2活性下调前后LM-MCF-7细胞中Lyso PC和PC含量的变化,发现其中4种PC可被c PLA2水解产生AA.还发现,细胞内Lyso PC与PC的比值可以反映c PLA2的活性.通过以上研究进一步证实了由c PLA2活性调节的AA释放及代谢对乳腺癌转移具有重要作用.
We have previously reported that arachidonic acid (AA) metabolites can promote the proliferation and migration of breast cancer cells.In order to further find out the endogenous mechanism of maintaining AA high level metabolism in highly metastatic breast cancer cells, We used HPLC / ESI / MSn to detect and analyze lysophosphatidylcholines (Lyso PCs) and phosphatidylcholines in breast cancer MCF-7 and high metastatic breast cancer LM-MCF-7 cells The contents and contents of phosphatidylcholines (PCs) were investigated. The contents of 10 kinds of Lyso PC were found to be significantly higher than that of MCF-7 cells in LM-MCF-7 cells and 6 kinds of PC were hydrolyzed to produce AA, -7 cells was significantly lower than that of MCF-7 cells, suggesting that elevated lysophospholipids and decreased phospholipid content may be associated with breast cancer metastasis in LM-MCF-7 cells, COX-2 inhibitor indole Indomethacin and nordihydroguaiaretic acid (NDGA) could significantly reduce the activity of c PLA2. HPLC-ESI-MSn was used to compare the changes of Lyso PC and Lyso in LM-MCF-7 cells before and after PLA activity was decreased PC content changes, found it Four kinds of PC could be hydrolyzed by c PLA2 to generate AA.It was also found that the intracellular ratio of Lyso PC to PC could reflect the activity of c PLA2.The above results further confirmed that AA release and metabolism regulated by c PLA2 activity have the following effects on breast cancer metastasis: Important role.