N-myc下游调节基因2在子宫内膜癌组织中表达及意义

目的探讨N-myc下游调节基因2(N-myc downstream-regulatedgene 2,NDRG2)在子宫内膜癌组织中的表达,及对肿瘤细胞增殖、侵袭的影响。方法行根治性切除术子宫内膜癌患者77例,手术切除的肿瘤组织为子宫内膜癌组,癌旁正常组织为癌旁组,采用实时荧光定量PCR法检测2组NDRG2基因表达,并分析其表达与临床病理特征的关系。将对数生长期子宫内膜癌HEC-1A细胞随机分为NDRG2抑制组(转染NDRG2干扰序列)、NDRG2正常表达组(转染NDRG2干扰对照序列)、空白对照组(不作任何处理),采用实时荧光定量PCR法检测3组转染48 h NDRG2基因表达,CCK-8法检测3组转染48、96 h增殖活力,划痕试验检测3组转染后培养12、24 h迁移能力,Transwell小室法检测3组转染48 h侵袭能力。结果子宫内膜癌组NDRG2 mRNA相对表达量(1.30±0.11)低于癌旁组(1.95±0.15)(P<0.05);FIGO分期Ⅱ~Ⅳ期、中低分化、有淋巴结转移者NDRG2 mRNA相对表达量(1.16±0.07、1.14±0.10、1.24±0.07)低于FIGO分期Ⅰ期、高分化、无淋巴结转移者(1.52±0.13、1.56±0.17、1.48±0.12)(P<0.05);转染48 h,NDRG2抑制组NDRG2 mRNA相对表达量(0.48±0.11)低于NDRG2正常表达组(1.07±0.08)、空白对照组(1.09±0.16);转染48、96 h,NDRG2抑制组增殖活力吸光度(optical density,OD)值(0.47±0.06、0.76±0.03)高于NDRG2正常表达组(0.33±0.07、0.58±0.03)、空白对照组(0.36±0.08、0.61±0.02)(P<0.05);NDRG2正常表达组、空白对照组转染48 h,NDRG2 mRNA相对表达量及转染48、96 h增殖活力OD值比较差异均无统计学意义(P>0.05);NDRG2抑制组转染后培养12、24 h划痕愈合率[(14.32±2.17)%、(34.28±4.95)%]及侵袭细胞数[(122.91±8.87)个]均高于NDRG2正常表达组[(7.14±1.52)%、(12.73±3.02)%、(104.21±2.94)个]、空白对照组[(6.82±1.24)%、(11.64±2.86)%、(99.71±5.40)个](P<0.05),NDRG2正常表达组与空白对照组比较差异无统计学意义(P>0.05)。结论NDRG2在子宫内膜癌组织中呈低表达,下调NDRG2基因表达可促进子宫内膜癌HEC-1A细胞增殖、迁移和侵袭。

Expression and significance of N-myc downstream-regulated gene 2 in endometrial cancer

Objective To investigate the expression of N-myc downstream-regulated gene 2(NDRG2)in endometrial cancer and its effect on tumor cell proliferation and invasion.Methods Real-time fluorescence quantitative PCR was used to detect the expressions of NDRG2 in the resected cancer tissue(cancer group)and the adjacent normal tissue(adjacent group)from 77 patients with endometrial cancer.The relationship between the expression of NDRG2 and clinicopathological features of endometrial cancer was analyzed.The endometrial cancer HEC-1 A cells in logarithmic growth phase were randomly divided into NDRG2 inhibition group transfected with NDRG2 interference sequence,NDRG2 normal expression group transfected with NDRG2 interference control sequence,and blank control group with no treatment.The expression level after 48 htransfection,proliferation activity after 48 and 96 htransfection,migration ability after 12 and 24 hculture and invasion ability of NDRG2 gene after 48 htransfection were detected using CCK-8 assay,scratch test and Transwell chamber assay,respectively.Results The relative expression level of NDRG2 mRNA was significantly lower in cancer group(1.30±0.11)than that in adjacent group(1.95±0.15)(P<0.05),lower in patients with FIGO phaseⅡ-Ⅳ(1.16±0.07),moderately and poorly differentiated(1.14±0.10)and lymph node metastasis(1.24±0.07)in cancer group than that in patients with FIGO stageⅠ(1.52±0.13),highly differentiated(1.56±0.17)and no lymph node metastasis(1.48±0.12)(P<0.05).The relative expression level of NDRG2 mRNA after 48 htransfection was significantly lower in NDRG2 inhibition group(0.48±0.11)than that in NDRG2 normal expression group(1.07±0.08)and blank control group(1.09±0.16)(P<0.05).The optical density values after 48 and 96 htransfection were significantly higher in NDRG2 inhibition group(0.47±0.06,0.76±0.03)than those in NDRG2 normal expression group(0.33±0.07,0.58±0.03)and blank control group(0.36±0.08,0.61±0.02)(P<0.05).The relative expression level after 48 htransfection and optical density values after 48 and 96 htransfection showed no significant differences between NDRG2 normal expression group and blank control group(P>0.05).The scratch healing rates after 12 and 24 hculture and the number of invasive cells were significantly higher in NDRG2 inhibition group((14.32±2.17)%,(34.28±4.95)%,122.91±8.87)than those in NDRG2 normal expression group((7.14±1.52)%,(12.73±3.02)%,104.21±2.94)and blank control group((6.82±1.24)%,(11.64±2.86)%,99.71±5.40)(P<0.05),and showed no significant differences between NDRG2 normal expression group and blank control group(P>0.05).Conclusion NDRG2 is lowly expressed in endometrial cancer tissues.Down-regulation of NDRG2 gene expression could promote cell proliferation and accelerate cell migration and invasion.