ATIP3a-HMGA2-ERK信号通路对卵巢上皮细胞癌顺铂耐药性的影响  

Effects of ATIP3a-HMGA2-ERK signaling pathway on cisplatin resistance in epithelial ovarian cancer

作　　者：黄平[1] 李彦英[1] 李玲玲 齐冰丽 苏梦亚[1] 张纪妍 HUANG Ping;LI Yan-ying;LI Ling-ling;QI Bing-li;SU Meng-ya;ZHANG Ji-yan(The First Department of Gynaecology,Cangzhou Central Hospital,Hebei Province,Cangzhou 061000,China)

机构地区：[1]河北省沧州市中心医院妇一科,河北沧州061000

出　　处：《河北医科大学学报》2018年第10期1179-1184,共6页Journal of Hebei Medical University

摘　　要：目的探讨血管紧张素Ⅱ受体的相互作用蛋白3a(angiotensinⅡtype 2receptor-interacting protein3a,ATIP3a)-高迁移率族蛋白A2(high mobility group AT-hook 2,HMGA2)-细胞外调节蛋白激酶(extracellular regulated protein kinase,ERK)信号通路对卵巢上皮细胞癌顺铂耐药性的影响。方法培养顺铂耐药卵巢癌细胞株SKOV3/DDP、A2780/DDP,分为8组(n=3),对照组C1和C2组仅向SKOV3/DDP、A2780/DDP细胞中加入RMPI 1640培养基,A1组和A2组为分别向SKOV3/DDP、A2780/DDP细胞中加入ATIP3a多肽(1nmol/L)处理6h,S1和S2组为分别向SKOV3/DDP、A2780/DDP细胞中转染siRNA-ATIP3a,VC1和VC2组分别向SKOV3/DDP、A2780/DDP细胞中转染siRNA-vector作为对照。顺铂3μg/mL处理72h后,采用乳酸脱氢酶法检测细胞的增殖能力,体外侵袭实验检测细胞侵袭能力,Real-time PCR法检测HMGA2mRNA表达,免疫蛋白印记法检测HMGA2和磷酸化ERK的表达。结果A1组SKOV3/DDP细胞增殖率和侵袭能力、HMGA2 mRNA和蛋白表达、磷酸化ERK蛋白表达明显低于C1组,S1组SKOV3/DDP细胞增殖率和侵袭能力、HMGA2mRNA和蛋白表达、磷酸化ERK蛋白表达明显高于C1组、A1组,VC1组SKOV3/DDP细胞增殖率和侵袭能力、HMGA2 mRNA和蛋白表达、磷酸化ERK蛋白表达高于A1组,低于S1组,差异均有统计学意义(P<0.05);A2组A2780/DDP细胞增殖率和侵袭能力、HMGA2mRNA和蛋白表达、磷酸化ERK蛋白表达低于C2组;S2组A2780/DDP细胞增殖率和侵袭能力、HMGA2 mRNA和蛋白表达、磷酸化ERK蛋白表达明显高于C2组、A2组,VC2组A2780/DDP细胞增殖率和侵袭能力、HMGA2mRNA和蛋白表达、磷酸化ERK蛋白表达高于A2组,低于S2组,差异均有统计学意义(P<0.05)。结论卵巢上皮细胞癌顺铂耐药性可能与ATIP3a-HMGA2-ERK信号通路有关。Objective To explore the effects of ATIP3 a-HMGA2-ERK signaling pathway on cisplatin resistance in epithelial ovarian cancer.Methods DDP-resistant ovarian cancer cell lines SKOV3/DDP and A2780/DDP were cultured to exponential phase and assigned to control group（C1 and C2 Group）,ATIP3 agroup（A1 and A2 Group）,siRNA-ATIP3 agroup（S1 and S2 Group）and siRNA-vector group（VC1 and VC2 Group）（n=3）,respectively.The cells in A1 and A2 groups were treated with ATIP3 apolypeptides（1 nmol/L）.The cells in S1 and S2 groups were treated with siRNA-ATIP3 a,but VC1 and VC2 were treated with siRNA-vector as control.Then all the cells were treated with DDP for 72 h.The effects of cell proliferation and invasion were assessed by lactate dehydrogenase and transwell assays.The expression in HMGA2 was measured by Real-time PCR and western-blot.Phosphorylation of ERK was also assessed by Western-blot.Results Compared with C1, ATIP3 a polypeptides treatment decreased cell proliferation,invasion,mRNA and protein expression of HMGA2,and phosphorylation of ERK in A1 group.Compared with C1 and A1 groups,siRNA-ATIP3 aincreased cell proliferation,invasion,mRNA and protein expression of HMGA2,and phosphorylation of ERK in S1 group.The cell proliferation,invasion,mRNA and protein expression of HMGA2,and phosphorylation of ERK in VC1 group were increased compared with A1,but decreased compared with S1.Compared with C2,ATIP3 apolypeptides treatment decreased cell proliferation,invasion,mRNA and protein expression of HMGA2,and phosphorylation of ERK in A1 group.Compared with C2 and A2 groups,siRNA-ATIP3 aincreased cell proliferation,invasion,mRNA and protein expression of HMGA2,and phosphorylation of ERK in S2 group.The cell proliferation,invasion,HMGA2 expression of mRNA and protein,and phosphorylation of ERK in VC2 group were increased compared with A2,but decreased compared with S2.Conclusion The DDP-resistant of human epithelial ovarian cancer might be associated with ATIP3 a-HMGA2-ERK signal pathway.

关 键 词：卵巢肿瘤 顺铂耐药性 ATIP3a-HMGA2-ERK信号通路 

分 类 号：R737.31[医药卫生—肿瘤]