磷脂酶A_2抑制剂对卵巢癌细胞转移潜能的影响

Effect of inhibitors of phospholipase A_2 on the metastasis potentials of human ovarian cancer cells

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。

AIM：It is important to find inhibitors for metastasis of ovarian cancer （OC）.OC cells （OCC） produce Lysophosphophatidic acid （LPA）,which promotes the OC development.Phospholipase A2 （PLA2） is responsible for LPA production.This study is to investigate the effect of PLA2 inhibitors on the metastasis of OC.METHODS：Cell migration and adhesion were measured by Transwell assay.The expression and activation of PLA2 were detected by Western blot.Invasion into the peritoneal monolayer was detected through ECIS.LPA concentration was measured by mass spectrum.Metastasis was detected through in vivo OC model.RESULTS：（1） LPA promoted the migration and adhesion of SKOV3 in a dose-dependent manner in vitro;（2） iPLA2 and cPLA2 expressed highly and activated in SKOV3.（3）AACOCF3 and HELSS significantly inhibited LPA secretion from SKOV3;（4）AACOCF3 and HELSS significantly inhibited the distant metastasis of SKOV3 in mude mice model.CONCLUSION：LPA significantly enhanced the migration,adhesion and invasion of SKOV3.AACOCF3 and HELSS significantly inhibited the LPA secretion,migration and invasion of SKOV3.They also inhibited the distant metastasis of SKOV3 in vivo.Our data suggest AACOCF3 and HELSS may be the potential inhibitors of metastasis of OC.