功能蛋白在氯化镧逆转卵巢癌顺铂耐药中的差异表达分析
摘要
目的从蛋白质水平研究氯化镧对人卵巢癌顺铂耐药细胞(COC1/DDP)功能蛋白表达的影响,为探讨氯化镧逆转卵巢癌顺铂耐药的机制提供实验依据。方法取对数生长期COC1/DDP细胞分为4组,对照组只加入10%胎牛血清培养基培养,顺铂组加入23.08μg/m L顺铂,氯化镧组和氯化镧+顺铂组分别加入1.5μmol/L氯化镧,处理8 h后氯化镧+顺铂组加入23.08μg/m L顺铂。采用蛋白印迹(Western blot)技术检测顺铂和氯化镧分别作用于COC1/DDP后,4组中ERCC1、Ki67、CDK6、HDAC2、c-Cbl和微管末端结合蛋白1(EB1)6种功能蛋白的表达变化。结果与对照组相比,COC1/DDP的4种功能蛋白ERCC1、Ki67、CDK6、c-Cbl在顺铂组和顺铂+氯化镧组中表达显著下调,差异有统计学意义(P<0.05);且顺铂+氯化镧组较顺铂组表达明显下调,差异有统计学意义(P<0.05)。与对照组比较,顺铂组中HDAC2和EB1表达明显下调,差异有统计学意义(P<0.05);顺铂+氯化镧组与顺铂组、氯化镧组中表达比较有下降趋势,但差异无统计学意义(P>0.05)。结论氯化镧可能通过多种途径下调ERCC1、Ki67、CDK6和c-Cbl表达,从而介导逆转卵巢癌顺铂耐药。
引文
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[5]Zhao YN,He DN,Wang YD,et al.Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer[J].Oncol Lett,2016,11(4):2925-2933.
[6]Li FY,Ren XB,Xie XY,et al.Meta-analysis of excision repair cross-complementation group 1(ERCC1)association with response to platinum-based chemotherapy in ovarian cancer[J].Asian Pac J Cancer Prev,2013,14(12):7203-7206.
[7]Ulker M,Duman BB,Sahin B,et al.ERCC1 and RRM1 as a predictive parameter for non-small cell lung,ovarian or pancreas cancer treated with cisplatin and/or gemcitabine[J].Contemp Oncol,2015,19(3):207-213.
[8]刘芯,李莹,邓秋华,等.可切除非小细胞肺癌ERCC1的表达与预后的关系[J].广东医学,2014,35(11):1710-1712.
[9]雷双根,余小芬,谢春伟,等.乳腺癌Ki67和CK5/6的表达及与临床病理特征的关系[J].广东医学,2013,34(19):2971-2974.
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[11]Goff BA,Ries JA,Els LP,et al.Immunophenotype of ovarian cancer as predictor of clinical outcome:evaluation at primary surgery and second-look procedure[J].Gynecol Oncol,1998,70(3):378-385.
[12]Polcher M.Changes in Ki-67 labeling indices during neo‐adjuvant chemotherapy for advanced ovarian cancer are associated with survival[J].Int J Gynecol Cancer,2010,20(4):555-560.
[13]Kato S,Schwaederle M,Daniels GA,et al.Cyclin-dependent kinase pathway aberrations in diverse malignancies:clinical and molecular characteristics[J].Cell Cycle,2015,14(8):1252-1259.
[14]Sherr CJ,Beach D,Shapiro GI.Targeting CDK4 and CDK6:From discovery to therapy[J].Cancer Discov,2016,6(4):353-367.
[15]Kim MG,Pak JH,Choi WH,et al.The relationship between cisplatin resistance and histone deacetylase isoform overexpression in epithelial ovarian cancer cell lines[J].J Gynecol Oncol,2012,23(3):182-189.
[16]Huang R,Langdon SP,Tse M,et al.The role of HDAC2 in chromatin remodelling and response to chemotherapy in ovarian cancer[J].Oncotarget,2015,800(1):14-14.
[17]付冲,胡建国.c-cbl基因沉默对卵巢癌SKOV3细胞增殖和侵袭的影响[J].重庆医学,2015,44(36):5061-5064.
[18]Chen HY,Yang YM,Stevens BM,et al.Inhibition of redox/Fyn/c-Cbl pathway function by Cdc42 controls tumour initiation capacity and tamoxifen sensitivity in basal-like breast cancer cells[J].EMBO Mol Med,2013,5(5):723-736.
[19]Qu X,Zhang Y,Li Y,et al.Ubiquitin ligase Cbl-b sensitizes leukemia and gastric cancer cells to anthracyclines by activating the mitochondrial pathway and modulating Akt and ERK survival signals[J].FEBS Lett,2009,583(13):2255-2262.
[20]Luo Y,Li D,Ran J,et al.End-binding protein 1 stimulates paclitaxel sensitivity in breast cancer by promoting its actions toward microtubule assembly and stability[J].Protein Cell,2014,5(6):469-479.