Qin Yiyu, Gong Wei, Zhang Mingdi, Wang Jiandong, Tang Zhaohui, Quan Zhiwei
Department of General Surgery, Xinhua Hospital, Affiliated to School of Medicine, Shanghai Jiaotong University, Shanghai, China.
PLoS One. 2014 Jul 10;9(7):e102084. doi: 10.1371/journal.pone.0102084. eCollection 2014.
Forkhead box L1 (FOXL1), considered as a novel candidate tumor suppressor, suppresses proliferation and invasion in certain cancers. However, the regulation and function of FOXL1 in gallbladder cancer (GBC) remains unclear.
FOXL1 expression at mRNA and protein levels in GBC tissues and cell lines were examined by RT-PCR, immunohistochemistry and western blot assay. FOXL1 expression in GBC cell lines was up-regulated by transfection with pcDNA-FOXL1. The effects of FOXL1 overexpression on cell proliferation, apoptosis, migration and invasion were evaluated in vitro or in vivo. In addition, the status of mediators involved in migration, invasion and apoptosis was examined using western blot after transfection with pcDNA-FOXL1.
FOXL1 was frequently downregulated in GBC tissues and cell lines. Its higher expression is associated with better prognosis, while its lower expression is correlated with advanced TNM stage and poor differentiation. FOXL1 overexpression in NOZ cells significantly suppresses cell proliferation, migration and invasion in vitro and tumorigenicity in nude mice. FOXL1 overexpression disrupted mitochondrial transmembrane potential and triggered mitochondria-mediated apoptosis in NOZ cells. In addition, FOXL1 overexpression suppressed ZEB1 expression and induced E-cadherin expression in NOZ cells.
Our findings suggested that dysregulated FOXL1 is involved in tumorigenesis and progression of GBC and may serve as a predictor of clinical outcome or even a therapeutic target for patients with GBC.
叉头框L1（FOXL1）被认为是一种新型的候选肿瘤抑制因子，在某些癌症中可抑制细胞增殖和侵袭。然而，FOXL1在胆囊癌（GBC）中的调控及功能仍不清楚。
采用逆转录聚合酶链反应（RT-PCR）、免疫组织化学和蛋白质印迹法检测GBC组织及细胞系中FOXL1在mRNA和蛋白质水平的表达。通过转染pcDNA-FOXL1上调GBC细胞系中FOXL1的表达。在体外或体内评估FOXL1过表达对细胞增殖、凋亡、迁移和侵袭的影响。此外，转染pcDNA-FOXL1后，用蛋白质印迹法检测参与迁移、侵袭和凋亡的介质状态。
FOXL1在GBC组织和细胞系中经常下调。其高表达与较好的预后相关，而低表达与晚期TNM分期和低分化相关。NOZ细胞中FOXL1过表达显著抑制体外细胞增殖、迁移和侵袭以及裸鼠的致瘤性。FOXL1过表达破坏了NOZ细胞的线粒体跨膜电位并触发线粒体介导的凋亡。此外，FOXL1过表达抑制了NOZ细胞中ZEB1的表达并诱导E-钙黏蛋白的表达。
我们的研究结果表明，FOXL1失调参与了GBC的肿瘤发生和进展，可能作为临床结果的预测指标，甚至是GBC患者的治疗靶点。
