【摘要】 背景与目的:细胞凋亡信号转导的关键是凋亡下游蛋白caspase-3的激活。有关caspase-3与人类非小细胞肺癌的研究已取得了很大的进展,但它与大鼠肺鳞癌的关系的研究未见报道。本研究探讨大鼠肺鳞癌癌变过程中细胞增殖与凋亡相关基因cas-pase-3和增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)的表达在癌变过程中的作用。方法:取60只Wistar大鼠,其中50只用化学致癌物3-甲基胆蒽(3-methylcholanthrene,MCA)及二乙基亚硝胺(diethyinitrosamine,DEN)碘油溶液于左肺叶支气管灌注以诱发大鼠肺鳞状细胞癌;另10只灌注碘油作为对照。用免疫组织化学SP法检测癌变过程中caspase-3和PCNA蛋白的表达;TUNEL法检测凋亡细胞。结果:对照组大鼠支气管粘膜上皮、癌前病变和肺鳞癌中,caspase-3蛋白表达的阳性评分均值分别为3.10±0.99、2.25±1.13、1.38±0.95;PCNA的平均增殖指数(PCNA-LI)分别为:14.10±5.02、28.13±8.72、41.88±14.24;平均凋亡指数(AI)分别为:0.60±0.52、2.06±0.85、2.26±1.14。肺鳞癌与对照组大鼠支气管粘膜上皮相比,其caspase-3蛋白阳性表达的差异有非常显著性(P<0.01),与癌前病变相比其caspase-3阳性表达的差异有显著性(P<0.05)。对照组大鼠支气管粘膜上皮为低增殖指数和低凋亡指数,分别与后更多还原

【Abstract】 BACKGROUND &OBJECTIVE: The activation of caspase 3 protein,located the downstream of apoptosis,is the key of cell apoptosis signal conduction. Caspase 3 is the most important performer in accelerating apoptosis in the caspase family. Much progress has been achieved in the study of caspase 3 and human non small cell lung cancer. This study was designed to investigate the effect of cellular proliferation and apoptosis related genes caspase 3 and proliferating cell nuclear antigen (PCNA), and to seek whether they could be chosen as molecular biology markers for lung cancer. METHODS: 3 Methylcholanthrene (MCA) and diethyinitrosamine (DEN) were used to induce lung squamous cell carcinoma by intra left lobar bronchial instillation in 50 Wistar rats. The other 10 rats instilled with iodized oil were regarded as control group. The expression of caspase 3 and PCNA were evaluated by SP immunohistochemistry during carcinogenesis. TUNEL(TDT mediated dUTP nick end labeling) method was used to examine apoptotic cells. RESULTS: For the rat bronchial epithelium cells in control group, precancerous lesions, and lung squamous cell carcinoma, positive coefficient values of caspase 3 protein were 3.10±0.99, 2.25±1.13, and 1.38±0.95 on average, respectively; the means of PCNA labeling index (PCNA LI)were 14.10±5.02, 28.13±8.72, and 41.88±14.24, respectively; the means of apoptotic index(AI) were 0.60±0.52, 2.06±0.85, and 2.26±1.14, respectively.Significant differences in caspase 3 protein expression were observed between bronchial epithelium in control group and lung squamous cell carcinoma (P< 0.01). Caspase 3 expression was showed stronger in precancerous lesions than that in lung cancer (P< 0.05). Low proliferation index and low AI were detected in rat bronchial epithelium region in control group,which were significant differences in precancerous lesions and lung cancer, respectively (P< 0.01). In 34 rats with lung squamous cell carcinoma, there was negative relationship between caspase 3 and PCNA LI (r=-0.7306, P< 0.01), so did it in AI and PCNA LI(r=-0.8127,P< 0.01), but there was no relationship between caspase 3 expression and AI(P >0.05). CONCLUSION: Loss of caspase 3 expression may be associated with the development of lung squamous cell carcinoma in Wistar rats, but it is not associated with AI. PCNA LI is an important marker for malignant progression of lung cancer.更多还原