Fat1蛋白在下咽癌中的表达及在侵袭转移过程中的作用

Expression of Fat1 in hypopharyngeal carcinoma tissues and its role in invasion and metastasis of the tumor

目的探讨Fat1蛋白在下咽癌中的表达及其生物学行为。方法应用免疫组织化学染色检测组织中Fat1蛋白的表达水平,采用Kaplan-Meier法分析Fat1蛋白的表达与下咽癌患者生存期的关系。siRNA干扰下咽癌Fadu细胞中Fat1蛋白的表达;Western blot法检测siRNA干扰后Fat1蛋白的表达;CCK-8实验检测细胞增殖能力;克隆形成实验检测细胞成瘤能力;划痕实验、Transwell小室实验检测其侵袭、迁移能力。结果 Fat1蛋白主要在胞浆中表达,在下咽癌复发病例中的表达强度明显低于未复发患者(P=0.001);低表达组患者总生存时间明显低于高表达组(P=0.001)。体外实验提示,siRNA下调Fat1蛋白后,Fadu细胞生长能力明显高于对照组(P=0.004),且细胞克隆数也明显高于对照组(P=0.001);此外,下调Fat1蛋白后,Fadu细胞的迁移能力高于对照组,且细胞穿越小室的细胞数明显高于对照组(P=0.000)。结论 Fat1蛋白表达下调提示下咽癌患者预后较差;Fat1蛋白能显著抑制下咽癌细胞的生长、增殖、侵袭、转移能力。

Objective To investigate the expression of Fat1 in hypopharyngeal carcinoma and its role in the biological behavior of the tumor. Methods The expression of Fatl was detected by immunohistochemical staining, and the correlation between the expression of Fatl and the survival time was analyzed by Kaplan-Meier survival analysis, siRNA was used to down-regulate Fatl expression in Fadu cells, the expression of Fatl protein was detected by Western blot; CCK-8 was used to evaluate cell proliferation. Clone forming test was used to estimate cell tumorigenicity, the invasion and migration ability were quantified by cell scratch test and transwell assay. Results Fatl protein was mainly expressed in cytoplasm, and the staining intensity patients with recurrence was significantly lower than that in those without recurrence （P = 0.001 ）. The overall survival time of strong expression group was significantly higher than that of weak expression group （P =0. 001 ）. Moreover, down-regulation of Fatl by siRNA enhanced the growing ability （P = 0. 004） and the number of cell clones （P = 0.001 ） in Fadu cells. In addition, down-regulation of Fatl promoted Fadu cells＇migration and invasion ability （P = 0. 000）. Conclusions Down-regulated expression of Fatl indicates poor prognosis in hypopharyngeal carcinoma. Fatl probably controls the growth, proliferation, invasion and metastasis of hypopharyngeal carcinoma cells.