TopoⅡα、RRM1在吡柔比星、吉西他滨治疗非肌层浸润性膀胱癌中的临床应用  

The clinical application of topoisomeraseⅡαand RRM1 in pirarubicin and gemcitabine in the treatment of non-muscular invasive bladder cancer

作　　者：邢力永 刘志飞[1] 朱研峰 Xing Liyong;Liu Zhifei;Zhu Yanfeng(Department of Urology,Tangshan People′s Hospital,Tangshan 063000,China)

机构地区：[1]唐山市人民医院泌尿外科,唐山063000

出　　处：《国际泌尿系统杂志》2023年第3期461-465,共5页International Journal of Urology and Nephrology

基　　金：河北省医学研究课题计划(20171274)。

摘　　要：目的探讨拓扑异构酶Ⅱα(TopoⅡα)和核糖核苷酸还原酶亚基M1(RRM1)与吡柔比星、吉西他滨药物治疗非肌层浸润性膀胱癌(NMIBC)中的效果。方法选取2018年1月至2021年1月在本院收治的85例NMIBC患者的临床资料,根据不同化疗药物行膀胱灌注治疗将患者分为吡柔比星组(45例)和吉西他滨组(40例)。通过转染TopoⅡαshRNA质粒在BIU-87细胞中敲除TopoⅡα(TopoⅡαshRNA组),并以未转染TopoⅡαshRNA质粒的BIU-87细胞作为对照(BIU-87对照组);通过转染RRM1 cDNA质粒在KK47细胞中过表达RRM1(PCDNA RRM1组),并以未转染RRM1 cDNA质粒的KK47细胞作为对照(KK47对照组)。采用免疫组化技术检测组织中的蛋白表达,采用逆转录-聚合酶链反应(qRT-PCR)和Western blot法检测细胞内的mRNA和蛋白水平。采用MTT法检测细胞的半抑制浓度值。结果在吡柔比星组中,TopoⅡα高表达患者的复发率为25%,而TopoⅡα低表达患者的复发率为61.5%(P<0.05)。吉西他滨组中,RRM1高表达的复发率为66.7%,而低表达的复发率为27.3%(P<0.05)。BIU-87细胞系中TopoⅡα、RRM1的mRNA和蛋白水平均高于KK47细胞系中水平(P=0.024、0.031)。与BIU-87对照组比较,TopoⅡαshRNA组的TopoⅡαmRNA和蛋白水平显著降低(P=0.012);与KK47对照组比较,PCDNA RRM1组的RRM1 mRNA和蛋白水平均升高(P=0.028)。吡柔比星对BIU-87和KK47细胞系的IC50值分别为(0.84±0.22)μg/mL和(1.82±0.31)μg/mL。吉西他滨对BIU-87和KK47细胞系的IC50值分别为(4.94±0.31)μg/mL和(3.45±0.32)μg/mL。结论TopoⅡα高表达或RRM1低表达可以预测吡柔比星或吉西他滨对NMIBC治疗的敏感性,对临床上选择更有效的化疗药物治疗NMIBC具有指导意义。Objective To investigate the effect of TopoⅡα,RRM1,pirarubicin and gemcitabine in the treatment of non-muscle invasive bladder cancer(NMIBC).Methods The clinical data of 85 patients with NMIBC admitted to our hospital from January 2018 to January 2021 were selected.According to different chemotherapy drugs,they were divided into pirarubicin group(45 cases)and gemcitabine group(40 cases).TopoⅡαwas knocked down in BIU-87 cells by transfection of TopoⅡαshRNA plasmid(TopoⅡαshRNA group),and BIU-87 cells without TopoⅡαshRNA plasmid transfection were used as control(BIU-87 control group).RRM1 was overexpressed in KK47 cells by transfection with RRM1 cDNA plasmid(PCDNA RRM1 group),and non-transfected KK47 cells were used as control(KK47 control group).Immunohistochemistry was used to detect the protein expression in the tissues,and reverse transcription-polymerase chain reaction(qRT-PCR)and Western blot were used to detect the mRNA and protein levels in the cells.MTT assay was used to detect the semi-inhibitory concentration of cells.Results In the pirarubicin treatment group,the recurrence rate of TopoⅡαhigh expression patients was 25%,while that of TopoⅡαlow expression patients was 61.5%(P<0.05).In gemcitabine group,the recurrence rate of RRM1 high expression group was 66.7%,while that of RRM1 low expression group was 27.3%(P<0.05).The mRNA and protein levels of TopoIIαand RRM1 in BIU-87 cell line were higher than those in KK47 cell line(P=0.024,0.031).Compared with the BIU-87 control group,the mRNA and protein levels of TopoIIαin the TopoⅡαshRNA group were significantly decreased(P=0.012).Compared with the KK47 control group,the mRNA and protein levels of RRM1 in the PCDNA RRM1 group were increased(P=0.028).The IC50 values of pirarubicin against BIU-87 and KK47 cells were(0.84±0.22)μg/mL and(1.82±0.31)μg/mL,respectively.The IC50 values of gemcitabine against BIU-87 and KK47 cell lines were(4.94±0.31)μg/mL and(3.45±0.32)μg/mL,respectively.Conclusions High expression of TopoⅡαor low

关 键 词：膀胱肿瘤 TopoⅡα RRM1 吡柔比星 吉西他滨 

分 类 号：R737.14[医药卫生—肿瘤]