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目的:卵巢癌细胞可分泌大量溶血性磷脂酸(LPA),LPA促进卵巢癌的发展,磷脂酶A2是LPA合成的主要酶。拟研究磷脂酶A2的抑制剂能否抑制卵巢癌的转移。方法:Transwell检测细胞迁移能力变化;Western blot检测磷脂酶A2的表达/活化状态;ECIS检测细胞浸润能力;质谱分析LPA浓度;裸鼠卵巢癌模型检测肿瘤的转移。结果:在体外LPA以剂量依赖方式促进SKOV3细胞的迁移和黏附;SK-OV3细胞内具有高表达和活化的iPLA2和cPLA2酶;应用AACOCF3和HELSS后,SKOV3分泌的LPA显著减少;AA-COCF3和HELSS显著抑制裸鼠内SKOV3的远地转移。结论:LPA显著促进SKOV3的迁移、黏附、对单层腹膜的浸润。AACOCF3和HELSS显著抑制SKOV3分泌LPA、并显著抑制SKOV3的迁移和浸润,还抑制裸鼠内SKOV3的远地转移,AACOCF3和HELSS有可能成为卵巢癌转移的潜在抑制剂。
OBJECTIVE: Ovarian cancer cells can secrete a large amount of hemolytic phosphatidic acid (LPA), which promotes the development of ovarian cancer. Phospholipase A2 is the major enzyme involved in LPA synthesis. To study whether inhibitors of phospholipase A2 can inhibit ovarian cancer metastasis. Methods: Transwell assay was used to detect the changes of cell migration. The expression of phospholipase A2 was detected by Western blot. The cell infiltration was detected by ECIS. The LPA concentration was detected by mass spectrometry. The ovarian cancer model was used to detect tumor metastasis. Results: In vitro, LPA promoted the migration and adhesion of SKOV3 cells in a dose-dependent manner. In the SK-OV3 cells, there were highly expressed and activated iPLA2 and cPLA2 enzymes. After treated with AACOCF3 and HELSS, LPA secreted by SKOV3 was significantly reduced. AA-COCF3 and HELSS significantly inhibited the distant metastasis of SKOV3 in nude mice. Conclusion: LPA can significantly promote SKOV3 migration, adhesion, monolayer peritoneal infiltration. AACOCF3 and HELSS significantly inhibited the secretion of LPA by SKOV3, significantly inhibited the migration and invasion of SKOV3, and also inhibited the distant metastasis of SKOV3 in nude mice. AACOCF3 and HELSS may be potential inhibitors of ovarian cancer metastasis.