血管生成样蛋白2在子宫内膜腺癌中的表达及作用研究

Expression of angiopoietin-like protein 2 in endometrial carcinoma and its implication

目的探究血管生成样蛋白2(ANGPTL2)在子宫内膜腺癌中的表达及对子宫内膜腺癌细胞增殖与成瘤的影响。方法选取2017年1月至2019年12月在温州市中西医结合医院或温州医科大学附属第一医院确诊子宫内膜腺癌、行子宫全切除术的子宫内膜腺癌组织标本60例,另择因子宫肌瘤行子宫全切除术的子宫内膜正常组织标本60例,采用实时荧光定量PCR法、Western blot法检测组织中ANGPTL2 mRNA、蛋白表达水平,并分析ANGPTL2 mRNA、蛋白表达水平与子宫内膜腺癌临床病理特征的关系。采用ANGPTL2敲除慢病毒感染子宫内膜腺癌细胞,分为ANGPTL2敲除组和对照组,观察并比较两组细胞ANGPTL2 mRNA、蛋白表达水平及增殖能力。将ANGPTL2敲除组和对照组细胞分别植入Nude小鼠皮下,观察并比较两组细胞成瘤情况。结果子宫内膜腺癌组织ANGPTL2 mRNA、蛋白表达水平均高于子宫内膜正常组织(均P<0.05)。ANGPTL2 mRNA表达水平与子宫内膜腺癌病理分级、临床分期均有关(均P<0.05),与患者绝经情况、雌激素受体(ER)、孕激素受体(PR)、BMI均无关(均P>0.05)。ANGPTL2蛋白表达水平与子宫内膜腺癌病理分级有关(P<0.05),与绝经情况、临床分期、ER、PR、BMI均无关(均P<0.05)。与对照组细胞相比,敲除组子宫内膜腺癌细胞ANGPTL2 mRNA、蛋白表达水平均下降(均P<0.05)。敲除组子宫内膜腺癌细胞增殖能力受抑制。敲除组细胞成瘤体积、重量均小于对照组(均P<0.05)。结论ANGPTL2在子宫内膜腺癌细胞中呈高表达,敲除ANGPTL2可抑制癌细胞增殖及体内成瘤能力,或可作为临床治疗子宫内膜腺癌的靶点。

Objective To investigate the expression of angiopoietin-like protein 2(ANGPTL2)in endometrial car-cinoma and its implication.Methods Sixty patients with endometrial adenocarcinoma underwent total hysterectomy in Wenzhou Integrated Traditional Chinese and Western Medicine Hospital and the First Affiliated Hospital of Wenzhou Medical University from January 2017 to December 2019 were enrolled in the study,and 60 normal endometrial tissue samples were taken from patients with hysteromyoma receiving total hysterectomy as control group.The relative expression ANGPTL2 mRNA was detected by real-time quantitative PCR.The expression of ANGPTL2 protein was detected by Western blot.The relationship between ANGPTL2 expression and clinical features of patients was analyzed.The expression of ANGPTL2 was Knocked-down in endometrial cancer cells as the study group,endometrial cancer cells with normal expression of ANGPTL2 served as the control group.The expression of ANGPTL2 mRNA and protein and the proliferation were detected.The Scramble/ANGPTL2-knockdown cells were inoculated in subcutaneous tissue of nude mice,the tumor growth was observed.Results The expression of ANGPTL2 mRNA and protein increased in endometrial carcinoma tissues compared with normal endometrium tissues.The expression of ANGPTL2 mRNA was significantly correlated with histological stage,clinical stage,but not correlated to the menopause status,estrogen receptor(ER),progesterone receptor(PR)levels and BMI of patients.The expression of ANGPTL2 protein was significantly correlated with histological stage,but not correlated to the menopause status,clinical stage,BMI,ER and PR levels.Compared with control group,the expression of ANGPTL2 mRNA and protein were decreased in the study group.The ability of tumor proliferation was decreased in the study group.The tumor growth in nude mice was decreased in study group.Conclusion The expression level of ANGPTL2 in endometrial carcinoma tissues is higher than that in normal endometrium tissues.The knock-down of ANGPTL2 could decrease the ability of proliferation and tumorigenesis.ANGPTL2 maybe used as one of the clinical therapeutic targets.