肿瘤抑制基因p53靶向α-L-岩藻糖苷酶1抑制前列腺癌增殖、迁移从而抑制前列腺癌的进展  

p53 targeted alpha-l-fucosidase 1 inhibits prostate cancer proliferation,migration and progression

作　　者：李冠儒[1] 张二伟[1] 李炎生[1] 王启[1] Li Guanru;Zhang Erwei;Li Yansheng;Wang Qi(Department of Urology,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450000,China)

机构地区：[1]郑州大学第一附属医院泌尿外科,450000

出　　处：《中华实验外科杂志》2022年第8期1538-1541,共4页Chinese Journal of Experimental Surgery

摘　　要：目的探索α-L-岩藻糖苷酶1(FUCA1)对前列腺癌增殖、迁移的影响及其作用机制。方法使用肿瘤基因组图谱(TCGA)数据库比较2006年至2021年497例前列腺癌和52例正常前列腺组织中基因FUCA1的差异表达。将人源的前列腺癌细胞系22RV1和DU145分为对照组和实验组, 分别转染空质粒和FUCA1质粒, 转染2 d后, 采用细胞计数试剂盒(CCK-8)、平板克隆形成实验、5-乙炔基-2’脱氧尿嘧啶核苷(EdU)染色实验验证细胞的增殖能力;采用划痕愈合实验和Transwell实验验证细胞的迁移能力, 采用蛋白质印迹法探索阿霉素以及抑癌基因p53与FUCA1的靶向关系。两实验组间比较采用独立样本t检验, 多实验组间比较采用方差分析。结果对照组细胞EdU着色细胞比例高于实验组[22RV1:(37.330±2.028)%比(16.000±2.646)%, t=6.400, P<0.05;DU145:(56.330±4.978)%比(27.330±2.404)%, t=5.246, P<0.05]、培养96h后吸光度高于实验组(22RV1:1.613±0.075比1.113±0.049, F=55.620, P<0.05;DU145:1.998±0.058比1.263±0.065, F=54.590, P<0.05)、克隆形成数高于实验组(22RV1:172.700±14.620比75.330±4.410, t=6.373, P<0.05;DU145:308.300±12.810比146.300±7.839, t=10.790, P<0.05)、划痕愈合率高于实验组[22RV1:(62.940±4.778)%比(25.700±4.948)%, t=5.414, P<0.05;DU145:(97.670±1.891)%比(38.430±2.727)%, t=17.860, P<0.05]、迁移细胞数高于实验组(22RV1:156.3±9.821比44.33±5.364, t=10.010, P<0.05;DU145:179±7.572比78.33±7.311, t=9.564, P<0.05)。抑癌基因P53过表达组FUCA1蛋白表达量高于对照组(22RV1:1.080±0.076比5.962±0.373, t=12.810, P<0.05;DU145:1.121±0.052比15.360±0.523, t=27.080, P<0.05)。结论 DNA损伤能够促进前列腺癌中FUCA1的表达, 同时, p53能够靶向FUCA1抑制前列腺癌细胞增殖和迁移从而抑制前列腺癌的进展。Objective To explore the effect of alpha-l-fucosidase 1(FUCA1)on the proliferation and migration of prostate cancer and its action mechanism.Methods Differential expression of gene FUCA1 in 497 prostate cancer and 52 paracancerous tissues was compared using the the cancer genome atlas(TCGA)database from 2006 to 2021.The human prostate cancer cell lines 22RV1 and DU145 were divided into control group and experimental group,and the vector and FUCA1 plasmid were transfected.After 2 days,the proliferation ability of cells was verified by cell counting kit-8(CCK-8)assay,plate cloning formation experiment and 5-Ethynyl-2′-deoxyuridine(EdU)staining experiment,while the migration ability of cells was verified by scratch healing experiment and Transwell experiment.The targeting relationship between doxorubicin and tumor suppressor gene p53 and FUCA1 was explored by Western blotting.The comparison between the two experimental groups was carried out using the independent sample t-test,and the comparison between the multi-experimental groups was analyzed by analysis of variance.Results The proportion of EdU-stained cells[22RV1:(37.330±2.028)%,(16.000±2.646)%,t=6.400,P<0.05;DU145:(56.330±4.978)%,(27.330±2.404)%,t=5.246,P<0.05],absorbance(22RV1:1.613±0.075,1.113±0.049,F=55.620,P<0.05;DU145:1.998±0.058,1.263±0.065,F=54.590,P<0.05),number of colony formation(22RV1:172.700±14.620,75.330±4.410,t=6.373,P<0.05;DU145:308.300±12.810,146.300±7.839,t=10.790,P<0.05),scratch healing rate[22RV1:(62.940±4.778)%,(25.700±4.948)%,t=5.414,P<0.05;DU145:(97.670±1.891)%,(38.430±2.727)%,t=17.860,P<0.05],and number of migrating cells(22RV1:156.3±9.821,44.33±5.364,t=10.010,P<0.05;DU145:179±7.572,78.33±7.311,t=9.564,P<0.05)were increased in the control group as compared with those in the experimental group.FUCA1 protein expression was higher in the tumor suppressor gene P53 overexpression group than in control group(22RV1:1.080±0.076,5.962±0.373,t=12.810,P<0.05;DU145:1.121±0.052,15.360±0.523,t=27.080,P<0.05).Conclusion DNA da

关 键 词：前列腺癌 α-L-岩藻糖苷酶1 P53 DNA损伤 

分 类 号：R737.25[医药卫生—肿瘤]