摘要
目的研究凋亡效应蛋白Caspase-3和凋亡抑制蛋白Survivin在大鼠肺鳞癌发生发展各阶段的基因转录、表达水平并探讨凋亡和肺癌发生发展的关系。方法选择Wistar大鼠40只,左肺下叶支气管灌注含三甲基胆蒽(3-Methylcholanthrene,MCA)和二乙基亚硝胺(Diethylinitrosamine,DEN)的碘油溶液0.1 ml,另8只灌注0.1 ml碘油做为对照,分批处死获取肺鳞癌形成过程各阶段标本。原位杂交法检测各阶段病变组织中Caspase-3 mRNA和Survivin mRNA的转录水平并采用半定量法进行评分。结果有多个阶段病变共存,共获取支气管黏膜上皮增生18例、不典型增生15例(含鳞状化生7例)、原位癌6例、侵袭癌7例、转移癌6例。正常对照组大鼠支气管黏膜上皮细胞Caspase-3 mRNA表达高于试验组,差异有统计学意义(P=0.043),其中鳞癌组与正常组相比,差异最显著(P=0.014);根据据原位杂交评分,在鳞癌组织中Survivin mRNA表达高于癌前病变组、增生组及正常组(P<0.05);在鳞癌组中转移癌和非转移组Survivin mRNA表达评分比较差异有统计学意义(P<0.05)。病变肺组织中,Survivin mRNA和Caspase-3 mRNA呈负相关(Pearson’s R=-0.647,P<0.05)。结论 Caspase-3 mRNA、Survivin mRNA与肺鳞癌的发生和发展相关,Survivin mRNA与Caspase-3mRNA呈负相关关系,从分子水平验证了Survivin主要通过作用于Caspase-3来阻断细胞的凋亡过程,促进癌变进程。
Objective To investigate the expression of Caspase-3 and Survivin in the carcinogenesis of lung squamous cell carcinoma in rat. Methods Forty-eight wistar rats were instilled with 3Methylcholanthrene（ MCA）and Diethylinitrosamine （ DEN）into the left lobarbranchus to induce lung squamous cell carcinoma,the other 8 rats instilled with iodized oil were regar-ded as control group. The specimens were obtained in every pathological phase durig the carcinogenesis. The expression of Caspase-3 mRNA and Survivin mRNA in each patholonical phases during the carcinogenesis were examined by hybridization in si-tu. The score of hybridization in situ was calculated by combining an estimate of the percentage of immunoreactive cells with that of the stain intensity. Results Sixty specimens with different patholonical phase during the carcinonenesis showed：18 cases of hyperplasia,15 cases of dysplasia（ including 7 cases of squamous metaplasia）,6 cases of carcinoma in situ,7 cases of invasive camcinoma and 6 cases of metastatic carcinoma. The Caspase-3 mRNA expression levels in control group were higher than those in the test group,there were significant differences（P=0. 043）,and the difference in the Caspase-3 mRNA expression levels was the most significant between squamous carcinogenesis group and control group（P=0. 014）. The Survivin mRNA expression levels in lung squamous cell carcinoma were higher than those in hyperplasia,precancerous lesions,and control group（ P ﹤0. 05）. In squamous cell carcinoma group,there was significant difference in the Survivin mRNA expression levels between meta-static carcinoma and non-metastasis carcinoma（P﹤0. 05）. In lung squamous cell carcinoma,the expression level of Caspase-3 mRNA was negative correlated with that of Survivin mRNA（ Pearson’s R= -0. 647,P﹤0. 05）. Conclusion Caspase-3 and Survivin play an important role in the carcinonenesis of rat lung squamous cell carcinoma. The expression of Survivin mRNA is negative correlated with that of Caspase-3 mRNA. Survivin may take part in blocking cell apoptosis by inhibition caspase-3 activi-ty,thereby promote the carcinonenesis of lung cancer.
出处
《临床医学》
CAS
2014年第9期112-114,F0003,共4页
Clinical Medicine
