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目的:探讨Survivin基因的表达在肺癌发生、发展中的作用及其与Caspase-3、Bcl-2蛋白表达的相互关系。方法:对13例正常支气管粘膜上皮、11列不典型增生、54例肺癌及12例淋巴结转移癌石蜡切片组织,应用原位分子杂交法检测Survivin mRNA的表达;用免疫组化S-P法检测Caspase-3、Bcl-2蛋白的表达。结果:肺癌、淋巴结转移癌中Survivin mRNA阳性率分别为74.07%及91.67%,显著高于正常支气管粘膜上皮及不典型增生中的阳性率7.69%及27.27%(P均<0.01);低分化、中分化肺癌中阳性率96%、75%较高分化30.76%显著升高(P<0.01,P<0.05)。TNM分期Ⅲ期病例中,Survivin mRNA表达阳性率92.31%高于Ⅰ+Ⅱ期病例的57.14%(P<0.01)。Survivin mRNA表达与Caspase-3蛋白表达呈负相关(P<0.01),与Bcl-2蛋白表达呈正相关(P<0.01)。结论:Survivin基因在非小细胞肺癌中表达上调,提示其通过抑制细胞凋亡,在肺癌癌变发生、发展中起重要作用,可能成为肺癌基因治疗的新靶点;Survivin基因通过与激活的Caspase-3结合,抑制其活性,从而阻止细胞凋亡,其阳性表达亦预示肿瘤有较高的侵袭性和不良预后;Survivin基因与凋亡抑制基因bcl-2的共同表达可能在肺癌中起协同作用。
Objective: To investigate the role of Survivin gene expression in the development and progression of lung cancer and its relationship with Caspase-3 and Bcl-2 protein expression. Methods: The expression of Survivin mRNA was detected by in situ hybridization in 13 cases of normal bronchial epithelium, 11 atypical hyperplasia, 54 cases of lung cancer and 12 cases of lymph node metastatic carcinoma. The expression of Survivin mRNA was detected by immunohistochemical SP method. The expressions of Caspase- 3, Bcl-2 protein expression. Results: The positive rates of Survivin mRNA in lung cancer and lymph node metastasis were 74.07% and 91.67%, respectively, which were significantly higher than those in normal bronchial mucosa epithelium and atypical hyperplasia (7.69% vs 27.27%, P <0.01) In moderately differentiated lung cancer, the positive rate was 96% and 75% higher than the high differentiation 30.76% (P <0.01, P <0.05). The positive rate of Survivin mRNA in TNM stage Ⅲ was 92.31% higher than 57.14% in stage Ⅰ + Ⅱ (P <0.01). Survivin mRNA expression was negatively correlated with Caspase-3 protein expression (P <0.01), and positively correlated with Bcl-2 protein expression (P <0.01). CONCLUSIONS: Survivin gene is up-regulated in non-small cell lung cancer, which suggests that Survivin gene may play an important role in the genesis and progression of lung cancer by inhibiting apoptosis. Survivin gene may be a new target of gene therapy for lung cancer. 3 binding, inhibit its activity, thereby preventing apoptosis, the positive expression also indicates that the tumor has a higher aggressiveness and poor prognosis; co-expression of Survivin and apoptosis inhibitor gene bcl-2 may play a synergistic role in lung cancer.