Claudin-3调节MEK/ERK信号通路对紫杉醇耐药卵巢癌细胞增殖、迁移和侵袭的影响  

The impacts of Claudin-3 on the proliferation, migration, and invasion of paclitaxel resistant ovarian cancercells by regulating the MEK/ERK signaling pathway

作　　者：宋艳敏 孙广宇 李聪先 SONG Yanmin;SUN Guangyu;LI Congxian(Gynecology Department of Cangzhou People’s Hospital,Cangzhou,Hebei 061000,China)

机构地区：[1]沧州市人民医院妇科,河北沧州061000

出　　处：《中国优生与遗传杂志》2023年第10期2040-2045,共6页Chinese Journal of Birth Health & Heredity

基　　金：河北省2021年度医学科学研究课题计划(20210129)。

摘　　要：目的 探讨紧密连接蛋白3(Claudin-3)调节MEK/ERK信号通路对紫杉醇(PTX)耐药卵巢癌(OC)细胞增殖、迁移和侵袭的影响。方法 检测Ovcar-3、Ovcar-3/PTX及IOSE80细胞中Claudin-3表达;将PTX耐药Ovcar细胞(Ovcar-3/PTX)随机分为对照组(Control)、阴性对照组(sh-NC)、转染质粒组(sh-Claudin-3)、MEK/ERK激活剂组(C16-PAF)、sh-Claudin-3+C16-PAF组,分别检测细胞增殖、迁移、侵袭和E-cadherin、N-cadherin、Vimentin及p-MEK、MEK、p-ERK、ERK蛋白表达。结果 Claudin-3在Ovcar-3/PTX细胞中的表达显著高于IOSE80与Ovcar-3(P<0.05);不同浓度的PTX均降低细胞存活率,且sh-Claudin-3组IC50显著低于sh-NC组(P<0.05);与sh-NC组比较,sh-Claudin-3组细胞克隆数、迁移、侵袭、N-cadherin、Vimentin、p-MEK/EMK、p-ERK/ERK显著降低,E-cadherin显著增加(P<0.05);与Control组比较,C16-PAF组细胞克隆数、迁移、侵袭、N-cadherin、Vimentin、p-MEK/EMK、p-ERK/ERK显著增加,E-cadherin显著降低(P<0.05);与C16-PAF组比较,sh-Claudin-3+C16-PAF组细胞克隆数、迁移、侵袭、N-cadherin、Vimentin、p-MEK/EMK、p-ERK/ERK显著降低,E-cadherin显著增加(P<0.05)。结论 Claudin-3在Ovcar-3/PTX细胞中呈高表达,沉默Claudin-3表达通过抑制MEK/ERK信号通路抑制细胞增殖、迁移和侵袭。Objective To investigate the impacts of Claudin-3 on the proliferation,migration,and invasion of paclitaxel resistant ovarian cancer(OC)cells by regulating the MEK/ERK signaling pathway.Methods The expression of Claudin-3 was detected in Ovcar-3,Claudin-3/PTX,and IOSE80 cells.PTX resistant cells(Ovcar-3/PTX)were randomly grouped into Control group,negative control group(sh-NC),transfected plasmid group(sh-Claudin-3),MEK/ERK activator group(C16-PAF),and sh-Claudin-3+C16-PAF group,cell proliferation,migration,invasion,and expression of E-cadherin,N-cadherin,Vimentin,p-MEK,MEK,p-ERK,and ERK proteins were detected.Results The expression of Claudin-3 in Ovcar-3/PTX cells was obviously higher than that in IOSE80 and Ovcar-3(P<0.05),different concentrations of PTX all reduced cell survival rate,and the IC50 of the sh-Claudin-3 group was obviously lower than that of the sh-NC group(P<0.05).Compared with the sh-NC group,the numbers of cell clones,migration,invasion,N-cadherin,Vimentin,p-MEK/EMK,p-ERK/ERK in the sh-Claudin-3 group were obviously reduced,and the E-cadherin was obviously increased(P<0.05).Compared with the Control group,the numbers of cell clones,migration,invasion,N-cadherin,Vimentin,p-MEK/EMK,p-ERK/ERK in the C16-PAF group were obviously increased,while the E-cadherin was obviously reduced(P<0.05).Compared with the C16-PAF group,the numbers of cell clones,migration,invasion,N-cadherin,Vimentin,p-MEK/EMK,p-ERK/ERK in the sh-Claudin-3+C16-PAF group were obviously reduced,and the E-cadherin was obviously increased(P<0.05).Conclusion Claudin-3 is highly expressed in Ovcar-3/PTX cells,silencing Claudin-3 expression can inhibit cell proliferation,migration,and invasion by inhibiting the MEK/ERK signaling pathway.

关 键 词：紧密连接蛋白3 促分裂原活化的蛋白激酶(MEK)/细胞外信号相关激酶(ERK)信号通路 紫杉醇耐药 卵巢癌 

分 类 号：R737.31[医药卫生—肿瘤]