大鼠舌黏膜癌变中黏着斑激酶的转录表达及其与细胞凋亡的关系研究

Research on the relationship between focal adhesion kinase mRNA expression and cell apoptosis during 4NQO-induced rat tongue carcinogenesis

目的观察舌黏膜癌变过程中黏着斑激酶(FAK)的mRNA表达变化及其与细胞凋亡的关系,初步探讨其与舌黏膜癌变的关系。方法用4-亚基硝氧喹啉(4NQO)诱导大鼠舌黏膜癌变,分别获取正常、异常增生(轻、中、重度)口腔黏膜和口腔鳞癌组织。采用半定量反转录聚合酶链反应(RT-PCR)检测各样本FAK的mRNA水平,用TUNEL法检测细胞凋亡水平。结果大鼠舌黏膜癌变过程中,与正常口腔黏膜相比,FAK的mRNA水平在轻、中、重度异常增生口腔黏膜中无显著变化,然而在鳞癌组织中明显增高,与其他各组间相比差异有统计学意义(P<0.05);在黏膜癌变过程中FAK的mRNA水平与细胞凋亡呈负相关(r=-0.581,P<0.05)。结论FAK参与了舌黏膜癌变过程,可能成为一个新的治疗靶点。

Objective To investigate the mRNA expression of focal adhesion kinase （FAK） during oral carcinogenesis and its relationship with cell apoptosis. Methods The rat tongue carcinogenesis was induced by water-soluble 4-nitroquinoline 1-oxide （4NQO）, and then normal mucosa, mild-dysplastic epithelia, moderate-dysplastic epithelia, severe-dysplastic epithelia and primary oral squamous cell carcinoma （OSCC） tissue were obtained. FAK mRNA levels were examined by means of semiquantitative RT-PCR. Apoptotic nuclei were examined by means of immunohistochemistry （TUNEL assay）. Results In the process of multistage carcinogenesis, FAK mRNA levels varied without statistical significance among different histopathological groups of normal mucosa, mild-dysplastic epithelia, moderate-dysplastic epithelia or severe-dysplastic epithelia in turn. However, FAK mRNA level increased significantly in OSCC tissues. Furthermore, negative associations were revealed between apoptotic index and FAK mRNA levels in course of oral carcinogenesis （r=-0.581,P〈0.05）. Conclusions Our results implicated a role of FAK in oral carcinogenesis. Inhibition of FAK might be a potential novel treatment strategy in OSCC.