机构地区:[1]海南医学院第二附属医院放疗科,海南省海口市570311 [2]海南医学院第二附属医院神经外科,海南省海口市570311
出 处:《广西医学》2022年第19期2250-2257,共8页Guangxi Medical Journal
基 金:海南省卫生健康行业科研项目(20A200133)。
摘 要:目的探讨T-钙黏蛋白与恶性胶质瘤发生、发展及放疗敏感性的关系。方法(1)取37例恶性胶质瘤患者的癌组织和癌旁组织,以及正常胶质细胞株HEB和胶质瘤细胞系U251、A172,检测其T-钙黏蛋白mRNA和蛋白的表达情况。比较不同T-钙黏蛋白表达情况的患者的中位生存期。(2)将U251细胞、A172细胞分别分为空白对照组、阴性对照组、T-钙黏蛋白过表达组,空白对照组细胞不进行转染,将质粒pcDNA3.1、pcDNA3.1-T-cadherin分别转染至阴性对照组、T-钙黏蛋白过表达组细胞。检测转染后各组U251、A172细胞的增殖、凋亡、迁移能力,T-钙黏蛋白、波形蛋白、E-钙黏蛋白的表达水平。对转染后各组U251、A172细胞进行放射干预后,检测细胞存活率和相对克隆数。将各组转染后的U251细胞皮下注射至裸鼠右侧腋窝处,观察注射部位的成瘤情况。结果(1)恶性胶质瘤组织中T-钙黏蛋白的mRNA表达水平和阳性表达率均低于癌旁组织;T-钙黏蛋白表达阴性患者中位生存期短于T-钙黏蛋白表达阳性患者(均P<0.05)。与正常胶质细胞株HEB相比,胶质瘤细胞系U251和A172中T-钙黏蛋白的mRNA和蛋白表达水平均下调(均P<0.05)。(2)与空白对照组、阴性对照组比较,T-钙黏蛋白过表达组U251与A172细胞的EdU阳性率均降低,细胞凋亡率升高,迁移细胞数减少,波形蛋白表达水平下调,而T-钙黏蛋白和E-钙黏蛋白表达水平均上调,4 Gy、6 Gy的γ射线照射后细胞存活率降低,6 Gy的γ射线照射后细胞相对克隆数减少(均P<0.05)。与空白对照组、阴性对照组比较,T-钙黏蛋白过表达组裸鼠的肿瘤体积缩小(均P<0.05)。结论T-钙黏蛋白在恶性胶质瘤中呈现异常低表达状态。过表达T-钙黏蛋白能够明显抑制恶性胶质瘤的发展,并提高其放疗敏感性,有利于改善患者预后。Objective To investigate the relation of T-cadherin with the occurrence,development and radiosensitivity of malignant gliomas.Methods(1)The cancerous and paracancerous tissues of 37 patients with malignant glioma,and normal glial cell strain HEB and glioma cell lines U251 and A172 were obtained,and their expressions of T-cadherin mRNA and protein were detected.The median survival time was compared between patients with different T-cadherin expressions.(2)U251 and A172 cells were assigned to the blank control group,negative control group or T-cadherin over-expression group.Cells in the blank control group did not received transfection,whereas plasmids of pcDNA3.1,pcDNA 3.1-T-cadherin were transfected to cells in the negative control group and T-cadherin over-expression group,respectively.The proliferation,apoptosis,and migration of U251 and A172 cells,and the expressions of T-cadherin,vimentin,and E-cadherin in various groups were detected after transfection.The survival rate of cells and relative number of clones of U251 and A172 cells in various groups were detected after radiological intervention.The right axilla of nude mice received injection of transfected U251 cells of various group subcutaneously,and the tumor formation at the injection site was observed.Results(1)The mRNA expression of T-cadherin and positive expression rate were all lower in malignant glioma tissues than in paracancerous tissues,and the median survival time was shorter in patients with negative expression of T-cadherin than in patients with positive expression of T-cadherin(all P<0.05).Compared with normal glial cell strain HEB,the mRNA and protein expressions of T-cadherin in glioma cell lines U251 and A172 were down-regulated(all P<0.05).(2)Compared with the blank control group and negative control group,the EdU positive rates of U251 and A172 cells in the T-cadherin over-expression group were decreased,the apoptosis rate of cells was elevated,the number of migrant cells was decreased,the expression of vimentin was down-regulated,where
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