【摘要】 目的研究非小细胞肺癌组织中核因子κB(nuclear Factor-κB,NF-κB)的活性及其与细胞增殖、自发性细胞凋亡的关系。方法 2006年5至10月收集30例非小细胞肺癌组织标本及15例肺癌患者癌旁5 cm 肺组织标本。NF-κB活性通过凝胶电泳迁移率改变试验(EMSA)检测,用 RT-PCR 和 Western blot 方法检测 CyclinD1含量,免疫组织化学染色法检测增殖细胞核抗原(PCNA)蛋白含量,TUNEL 法检测细胞凋亡。结果癌旁肺组织、鳞癌组织、腺癌组织中 NF-κB活性(吸光度,A 值)分别为24 826±3724、28 028±4204、35 425±5317,三组比较差异有统计学意义(F=78.96,P<0.01)。鳞癌组织、腺癌组织中 NF-κB活性高于癌旁肺组织中 NF-κB活性,腺癌组织中 NF-κB活性高于鳞癌组织中 NF-κB活性。健康肺组织、鳞癌组织、腺癌组织中 CyclinD1 mRNA 表达量分别为2.04±0.24、2.91±0.37、4.13±0.36,三组比较差异有统计学意义(F=62.43,P<0.01)。癌旁肺组织、鳞癌组织、腺癌组织中 CyclinD1蛋白表达量分别为0.31±0.06、0.43±0.07、0.58±0.08,三组比较差异有统计学意义(F=89.24,P<0.01)。癌旁肺组织、鳞癌组织、腺癌组织中 PCNA 蛋白表达量分别为0.32±0.09、0.42±0.10、0.54±0.16,三组比较差异明显。癌旁肺组织、鳞癌组织、腺癌组织中凋亡指数分别为(2.58±0.39)%、(2.27±0.34)%、(2.92±0.59)%,三组比较无明显差异。鳞癌组织中NF-κB活性与 CyclinD1 mRNA、CyclinD1蛋白、PCNA 蛋白均呈正相关(r 值分别为0.51、0.54和0.60,P 均<0.05);腺癌组织中 NF-κB活性与 CyclinD1 mRNA、CyclinD1蛋白、PCNA 蛋白均呈正相关(r 值分别为0.60、0.64和0.68,P 均<0.05);鳞癌、腺癌组织中 NF-κB活性与细胞凋亡指数无相关关系。结论在非小细胞肺癌组织中 NF-κB活性增高。非小细胞肺癌组织中 NF-κB的异常活化可能与细胞增殖有关,但不影响自发性细胞凋亡。更多还原

【Abstract】 Objective To investigate the nuclear factor(NF)-κB activity in human non-small cell lung cancer(NSCLC)tissues and to explore the correlation between NF-κB activity and cell proliferation, and between NF-κB activity and cell spontaneous apoptosis.Methods Thirty samples of non-small cell lung cancer tissues and 15 normal lung tissues were collected from May to October in 2006.NF-κB activation was determined by electrophoretic mobility shift assay(EMSA).CyclinD1 level was examined by RT-PCR and Western blot.Proliferation cell nuclear antigen(PCNA)protein was examined by immunohistochemical analysis.Spontaneous cell apoptosis was determined by the TUNEL method.Results There was significant difference(F=78.96,P<0.01)in NF-κB activity among normal lung tissue group(24 826±3724), squamous-eell carcinoma tissue group(28 028±4204),and adenocarcinoma tissue group(35 425± 5317).The NF-κB activity in the squamous-cell carcinoma group and the adenocarcinom tissue group was higher than that in the normal lung tissue group(all P<0.01);and the NF-κB activity in the adenocarcinoma tissue group was higher compared with that in the squamous-cell carcinoma group(P< 0.05).There was significant difference(F=62.43,P<0.01)in the cyclinD1 mRNA level among normal lung tissue group(2.04±0.24),the squamous-cell carcinoma group(2.91±0.37),and the adenoearcinoma group(4.13±0.36).There was significant difference(F=89.24,P<0.01)in cyclinD1 protein level among normal lung tissue group(0.31±0.06),the squamons-cell carcinoma group(0.43± 0.07),and the adenocarcinoma group(0.58±0.08).There was significant difference(F=45.61,P< 0.01)in PCNA protein level among the normal lung tissue group(0.32±0.09),the squamous-cell carcinoma group(0.42±0.10),and the adenocarcinima group(0.54±0.16).There was no significant difference(F=1.86,P>0.05)in apoptosis index among the normal lung tissue group(2.58±0.39)%, the squamous-eell carcinoma group(2.27±0.34)%,and the adenocarcinoma group(2.92±0.59)%. The NF-κB activity was positively correlated with cyclin D1 mRNA level,cyclinD1 protein level,and PCNA protein level in the squamous-cell carcinoma group(r=0.51,0.54,0.60,all P<0.05),respectively;the NF-κB activity was also positively correlated with cyelinD1mRNA,cyclinD1 protein level,and PCNA protein level in the adenocarcinoma group(r=0.60,0.64,0.68,all P<0.05),respectively.The NF-κB activity in the squamous-cell group and the adenocarcinoma group was not related to cell apoptosis index. Conclusion NF-κB activity is increased in NSCLC tissues.Abnormal NF-κB activation may be associated with cell proliferation,but do not affect spontaneous cell apoptosis in NSCLC tissues.更多还原