乌苯美司对卵巢癌A2780细胞的生物学影响  

Biological effects of ubenimex on ovarian cancer A2780 cell

作　　者：关红卫 李娟[1] 孙锐 刘婕 李长忠[1] GUAN Hongwei;LI Juan;SUN Rui;LIU Jie;LI Changzhong(Department of Gynecology,Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,Shandong,China)

机构地区：[1]山东大学附属省立医院妇科

出　　处：《山东大学学报（医学版）》2019年第12期46-51,共6页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(81671434,81503298)

摘　　要：目的研究乌苯美司对卵巢癌A2780细胞增殖、细胞周期、凋亡和自噬以及迁移和侵袭能力的影响,探讨可能的作用机制。方法 CCK-8实验检测乌苯美司对A2780细胞增殖的影响;Transwell实验检测乌苯美司对A2780细胞迁移及侵袭能力的影响;流式细胞术检测乌苯美司对A2780细胞凋亡和细胞周期的影响;Western blotting检测APN、AKT、p-AKT、LC3B、p62表达水平的变化。结果①乌苯美司能够抑制A2780细胞的增殖(F浓度=812.56,P<0.001;F时间=8.58,P=0.010;F交互=4.00,P=0.027)、迁移(t=56.9,P<0.001)和侵袭(t=11.8,P<0.001)、导致G2/M期细胞比例增高(t=7.9,P=0.016),G1期细胞比例减少(t=14.8,P=0.005),发生G2/M细胞周期阻滞。②乌苯美司能够诱导A2780细胞凋亡(P=0.002),且联合应用AKT抑制剂后诱导细胞凋亡的作用增强(P=0.007)。③乌苯美司可以导致APN表达降低,p-AKT、LC3-B和p62表达增加。结论乌苯美司可能是卵巢癌的一种治疗方法或者辅助治疗方法,与AKT抑制剂联用能够增强其治疗效果。Objective To investigate the effect of ubenimex on cell proliferation, cell cycle, apoptosis, autophagy, migration and invasion in ovarian cancer A2780 cell and its possible mechanism. Methods CCK-8 assay was used to analyze the effect of ubenimex on proliferation of A2780 cell. Transwell assay was performed to detect the effect of ubenimex on migration and invasion of A2780 cell. Flow cytometry was used to analyze the cell apoptosis and cell cycle. Western blotting was performed to investigate the protein expression levels of APN, AKT, p-AKT, LC3-B, and p62. Results ①Ubenimex inhibited A2780 cell proliferation(Fconcentration=812.56,P<0.001;Ftime=8.58,P=0.010;Fconcentration×time=4.00,P=0.027), migration(t=56.9, P<0.001) and invasion(t=11.8, P<0.001), increased the cell proportion in G2/M phase(t=7.9, P=0.016) and decreased the cell proportion in G1 phase(t=14.8, P=0.005) which led to G2/M cell cycle arrest. ②Ubenimex induced A2780 cell apoptosis(P=0.002), and cell apoptosis was increased when ubenimex was combined with AKT inhibitor(P=0.007). ③Ubenimex reduced the APN expression, but increased p-AKT, LC3 B and p62 expressions. Conclusion Ubenimex may be a treatment or adjuvant therapy for ovarian cancer, and its therapeutic effect can be enhanced in combination with AKT inhibitor.

关 键 词：卵巢癌 乌苯美司 增殖 侵袭 凋亡 自噬 

分 类 号：R737.31[医药卫生—肿瘤]