细丝蛋白C对前列腺癌细胞迁移和侵袭的影响  

Effects of filamin C on migration and invasion of prostate cancer cells

作　　者：孙振业 宋斌 王磊 宋多 高闫尧 杨帆 SUN Zhenye;SONG Bin;WANG Lei;SONG Duo;GAO Yanyao;YANG Fan(Department of Urology,Second Affiliated Hospital of Air Force Medical University,Xi’an 710032,China)

机构地区：[1]空军军医大学第二附属医院泌尿外科,西安710032

出　　处：《山西医科大学学报》2022年第12期1511-1518,共8页Journal of Shanxi Medical University

基　　金：陕西省重点研发计划项目(2021SF-054)。

摘　　要：目的探讨细丝蛋白C(filamin C,FLNC)对前列腺癌细胞迁移和侵袭的影响。方法通过免疫组织化学分析了30例前列腺癌患者的癌组织及配对癌旁组织中FLNC的表达。根据FLNC蛋白的表达水平将30例前列腺癌患者分为FLNC低表达组(0~3分,n=9)和FLNC高表达组(4~12分,n=21),采用Kaplan-Meier法进行生存分析。对人前列腺癌细胞系(PC-3)转染抑制FLNC表达的小干扰RNA(siRNA-FLNC组)和阴性对照(siRNA-NC组),未转染的细胞作为对照组。通过MTT法检测细胞活力,Transwell实验进行迁移和侵袭分析。通过qRT-PCR或Western blot检测细胞中FLNC、Eotaxin-1、CCR3、p-ERK1/2、t-ERK1/2和MMP-3的表达。结果与癌旁组织相比,前列腺癌组织中FLNC的染色评分升高(1.43±0.86 vs 5.63±2.91,P<0.001)。FLNC低表达组和高表达组患者的TNM分期、淋巴结转移和生存时间差异有统计学意义(P<0.05)。与对照组相比,siRNA-FLNC组PC-3细胞中FLNC的mRNA和蛋白水平均降低(P<0.05),细胞活力降低(P<0.05),细胞迁移和侵袭数量降低(P<0.05)。与对照组相比,siRNA-FLNC组Eotaxin-1、CCR3、p-ERK1/2和MMP-3的蛋白相对表达量均降低(P<0.05),而t-ERK1/2的蛋白相对表达量无明显变化(P>0.05)。结论FLNC在前列腺癌组织中高表达并且与患者预后相关。沉默FLNC可能通过抑制Eotaxin-1-CCR3-ERK1/2-MMP-3通路降低前列腺癌细胞的迁移和侵袭能力。Objective To investigate the effect of filamin C(FLNC)on the migration and invasion of prostate cancer cells.Methods The expression of FLNC in cancer tissues and paired adjacent tissues of 30 patients with prostate cancer was analyzed by immunohistochemistry.Thirty patients with prostate cancer were divided into FLNC low expression group(0-3 scores,n=9)and FLNC high expression group(4-12 scores,n=21).Kaplan-Meier method was used for survival analysis.The human prostate cancer cell line PC-3 was transfected with small interfering RNA in siRNA-FLNC group and negative control in siRNA-NC group,and the untransfected cells were used as control group.Cell viability was detected by MTT assay,and migration and invasion abilities were determined by Transwells assay.The expression of FLNC,Eotaxin-1,CCR3,p-ERK1/2,t-ERK1/2 and MMP-3 in cells was detected by qRT-PCR or Western blot.Results The FLNC staining score in prostate cancer tissues was significantly higher than that in adjacent tissues(1.43±0.86 vs 5.63±2.91,P<0.001).There was significant difference in TNM stage,lymph node metastasis and survival time between low FLNC expression group and high FLNC expression group(P<0.05).Compared with control group,the levels of FLNC mRNA and protein in PC-3 cells were decreased in siRNA-FLNC group(P<0.05),the cell viability was decreased(P<0.05),and the numbers of cell migration and invasion were decreased(P<0.05).Compared with control group,the relative protein expression levels of Eotaxin-1,CCR3,p-ERK1/2 and MMP-3 were decreased in siRNA-FLNC group(P<0.05),while the relative protein expression of t-ERK1/2 had no significant change(P>0.05).Conclusion FLNC is highly expressed in prostate cancer tissue and is associated with patient prognosis.Silencing FLNC may reduce the migration and invasion abilities of prostate cancer cells by inhibiting the Eotaxin-1-CCR3-ERK1/2-MMP-3 pathway.

关 键 词：细丝蛋白C 前列腺癌 预后 迁移 侵袭 Eotaxin-1-CCR3-ERK1/2-MMP-3通路 

分 类 号：R737.25[医药卫生—肿瘤]