【摘要】 目的 探究烯醇化酶1 (ENO1)单克隆抗体（mAb）纳米颗粒联合谷氨酰胺酶抑制剂CB-839对宫颈癌HeLa细胞增殖和迁移的协同作用。方法 利用癌症基因组图谱分析正常宫颈组织和宫颈癌组织中糖酵解途径和谷氨酰胺代谢关键酶的表达差异。采用四甲基偶氮唑盐法观察叶酸修饰的聚乳酸-羟基乙酸（PLGA）-ENO1 mAb纳米颗粒和CB-839联合后对宫颈癌HeLa细胞增殖的影响。通过划痕损伤修复实验观察PLGA-ENO1 mAb和CB-839对宫颈癌HeLa迁移能力的影响；通过代谢试剂盒测定方法检测抑制糖酵解途径和谷氨酰胺代谢对HeLa细胞胞内还原型谷胱甘肽、谷氨酸的影响。结果 宫颈癌HeLa细胞存在谷氨酰胺依赖现象，并呈时间和剂量依赖性。与对照组比较，谷氨酰胺酶抑制剂CB-839抑制宫颈癌HeLa细胞的增殖（P <0.05），并具有剂量效应；PLGA-ENO1 mAb和CB-839联合应用，联合指数CI <1，表现出协同作用；CB-839未表现出抑制HeLa细胞迁移作用（P> 0.05），而和PLGA-ENO1 mAb联合应用后，可显著抑制迁移能力（P<0.01）；两药联用后胞内还原型谷胱甘肽和谷氨酸含量显著降低（P<0.05）。结论 PLGA-ENO1mAb和CB-839联合应用可有效抑制宫颈癌HeLa细胞的增殖和迁移。更多还原

【Abstract】 Objective To investigate the synergistic effect of enolase1(ENO1) monoclonal antibody(mAb)nanoparticles combined with glutaminase inhibitor CB-839 on the proliferation and migration of cervical cancer HeLa cells. Methods The expression differences of the glycolytic pathway and key enzymes of glutamine metabolism in normal cervical tissues and cervical cancer tissues were analyzed by cancer genome map.MTT method was used to observe the effect of PLGA(polylactic-glycolic acid)-ENO1 mAb nanoparticles combined with CB-839 on the proliferation of cervical cancer HeLa cells. The effects of PLGA-ENO1mAb nanoparticles and CB-839 on HeLa migration of cervical cancer were observed by scratch repair experiment.The effects of the inhibitory glycolytic pathway and glutamine metabolism on reduced glutathione and glutamate in HeLa cells were detected by a metabolic kit assay. Results Glutamine-dependent phenomenon existed in cervical cancer HeLa cells in a time-and dose-dependent manner. Compared with the blank group, glutamine inhibitor CB-839 inhibited the proliferation of cervical cancer HeLa cells in a dose-dependent manner,and the combination index CI < 1 of PLGA-ENO1 mAb and CB-839 showed a synergistic effect; CB-839 did not inhibit the migration of HeLa cells(P > 0.05), but combined with PLGA-ENO1 mAb nanoparticles could significantly inhibit the migration ability(P < 0.01). The contents of reduced glutathione and glutamate decreased significantly after the combination of the two drugs(P < 0.05). Conclusion The combination of multi-functional PLGA-ENO1 mAb and CB-839 can effectively inhibit the proliferation and migration of cervical cancer HeLa cells.更多还原