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乳腺癌转移中的磷脂酰胆碱和溶血磷脂酰胆碱分析
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药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系,天津大学化工学院,药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系,药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系,药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系,药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系,药物化学生物学国家重点实验室，南开大学生命科学学院，生物化学与分子生物学系

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天津市自然科学基金(14JCZDJC32800)，国家重点基础研究发展计划(973)(2015CB553905)，国家高技术研究发展计划(863)(2014AA020903)和国家自然科学基金(81372186)资助项目


Analysis of Phosphatidylcholines (PCs) and Lysophosphatidylcholines (LysoPCs) in Metastasis of Breast Cancer Cells
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State Key Laboratory of Medicinal Chemical Biology,Department of Biochemistry,College of Life Sciences,Nankai University,Department of Pharmaceutical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, P.R. China,State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China,State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China,State Key Laboratory of Medicinal Chemical Biology, Department of Cancer Research, College of Life Sciences, Nankai University, Tianjin 300071, China,State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China,State Key Laboratory of Medicinal Chemical Biology, Department of Biochemistry, College of Life Sciences, Nankai University, Tianjin 300071, China

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This work was supported by grants from Tianjin Natural Scientific Foundation (14JCZDJC32800), National Basic Research Program of China (2015CB553905), Hi-Tech Research and Development Program of China (2014AA020903) and The National Natural Science Foundation of China (81372186)

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    摘要:

    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，LysoPCs）和磷脂酰胆碱（phosphatidylcholines，PCs）的成分和含量。我们发现了10种LysoPC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cPLA2的活性，应用HPLC-ESI-MSn技术比较cPLA2活性下调前后LM-MCF-7细胞中LysoPC和PC含量的变化，发现其中4种PC可被cPLA2水解产生AA。我们还发现，细胞内LysoPC与PC的比值可以反映cPLA2的活性。通过以上研究我们进一步证实了由cPLA2活性调节的AA释放及代谢对乳腺癌转移具有重要作用。

    Abstract:

    The important role of phospholipids in many processes including cell cycle regulation, inflammation and tumorigenesis is increasingly becoming the focus of research. Previously we found that cytosolic phospholipase A2 (cPLA2) is over-expressed in breast cancer cells. Here, we assessed the profiles of phosphatidylcholines (PCs) and lysophosphatidylcholines (LysoPCs) that were mediated by cPLA2 in breast cancer cells. MCF-7 and LM-MCF-7 (with high metastatic potential) cell lines were used as models and the profiles of phospholipids were analyzed by HPLC/ESI/MSn. Our results showed that the levels of 10 species of LysoPCs were higher in LM-MCF-7 cells than that in MCF-7 cells. Meanwhile, six species of PCs that may produce arachidonic acid (AA) and associated LysoPCs were lower in LM-MCF-7 cells than that in MCF-7 cells. Furthermore, we identified that 4 out of 6 species of PCs were responsible for the generation of AA mediated by cPLA2 in LM-MCF-7 cells. The increased ratio of LysoPCs to PCs corresponds to the activation level of cPLA2. Thus, we conclude that 4 identified species of PCs and 4 corresponding species of LysoPCs mediated by cPLA2, as well as the up-regulation and activation of cPLA2, may involve in the metastasis of breast cancer cells.

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尤嘉琮,杨杰,方润平,胡楠,张晓东,张伟英,叶丽虹.乳腺癌转移中的磷脂酰胆碱和溶血磷脂酰胆碱分析[J].生物化学与生物物理进展,2015,42(6):563-573

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  • 收稿日期:2015-01-27
  • 最后修改日期:2015-04-29
  • 接受日期:2015-04-30
  • 在线发布日期: 2015-06-24
  • 出版日期: 2015-06-20
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