Chen Wei, Yuan Kun, Tao Ze-Zhang, Xiao Bo-Kui
Department of Otolaryngology-Head and Neck Surgery, The Central hospital of Wuhan, Wuhan, China.
Asian Pac J Cancer Prev. 2011;12(7):1785-8.
The transcription factor, Forkhead Box M1 (FoxM1), has a specific expression pattern during the cell cycle. It also plays an important role in cellular developmental pathways and in the maintenance of homeostasis between cell proliferation and apoptosis. However, the precise role and molecular mechanisms associated with FoxM1 in laryngeal squamous carcinoma remain unclear. Therefore, laryngeal squamous carcinoma cells were transfected with FoxM1-targeted small interfering RNA (siRNA) and compared with cells transfected with a control siRNA. Assays of these two treatment groups detected a decrease in cell viability associated with down-regulation of FoxM1 expression, and resulted in an inhibition of cell proliferation, migration, and invasion. These phenotypes were also associated changes in expression of VEGF and MMP-2, a decrease in expression of cyclin B, and an increase in expression of p27. These findings suggest that deregulation of FoxM1 protein signaling is sufficient to affect tumorigenesis and cancer progression. These results also indicate that inhibition of FoxM1 represents an attractive target for cancer therapy.
转录因子叉头框M1(FoxM1)在细胞周期中具有特定的表达模式。它在细胞发育途径以及细胞增殖与凋亡之间的稳态维持中也发挥着重要作用。然而,FoxM1在喉鳞状细胞癌中的确切作用和分子机制仍不清楚。因此,用靶向FoxM1的小干扰RNA(siRNA)转染喉鳞状癌细胞,并与用对照siRNA转染的细胞进行比较。对这两个治疗组的检测发现,细胞活力下降与FoxM1表达下调有关,并导致细胞增殖、迁移和侵袭受到抑制。这些表型还与VEGF和MMP-2表达的变化、细胞周期蛋白B表达的降低以及p27表达的增加有关。这些发现表明,FoxM1蛋白信号失调足以影响肿瘤发生和癌症进展。这些结果还表明,抑制FoxM1是癌症治疗的一个有吸引力的靶点。