Wang Pei, Ma Hongbing, Li Yong, Chen Dong, Li Xiaohui, Gao Xiang
Department of Cardiothoracic Surgery, Huaihe Hospital of Henan University Baobei Road No. 8 Kaifeng 475000 China
RSC Adv. 2018 Oct 2;8(59):33786-33793. doi: 10.1039/c8ra06041j. eCollection 2018 Sep 28.
Lung cancer begins in the lung and is a leading cause of premature death. Forkhead box C1 (FOXC1) has been reported to play an important role in different types of cancer, and evidence suggests that FOXC1 is highly expressed in non-small cell lung cancer (NSCLC) patients. However, the function and molecular mechanism of FOXC1 in the NSCLC cell line A549 is still unclear. In the present study, we indicate that FOXC1 is expressed in the NSCLC cell lines A549, H460, and SK-MES-1 at a high level compared with control human bronchial epithelial (HBE) cells. FOXC1 silencing promotes A549 cell apoptosis, whereas it inhibits cell survival. The levels of anti-apoptosis protein Bcl-2 decreased and the expression of pro-apoptosis protein Bax increased in FOXC1 silenced cells. Further studies show that FOXC1 knockdown inhibits the PI3K/AKT/hedgehog/Gli2 pathway. Overexpressed AKT or Gli2 reversed the effects of FOXC1 silencing on A549 cell survival and apoptosis. Taken together, our results conclude that FOXC1 silencing reduced the survival of cancer cells and promoted their apoptosis, and that the PI3K/AKT/hedgehog/Gli2 pathway plays an important role in the functioning of FOXC1 silencing.
肺癌起源于肺部，是导致过早死亡的主要原因。据报道，叉头框C1（FOXC1）在不同类型的癌症中起重要作用，且有证据表明FOXC1在非小细胞肺癌（NSCLC）患者中高表达。然而，FOXC1在NSCLC细胞系A549中的功能和分子机制仍不清楚。在本研究中，我们发现与对照人支气管上皮（HBE）细胞相比，FOXC1在NSCLC细胞系A549、H460和SK-MES-1中高表达。FOXC1沉默可促进A549细胞凋亡，而抑制细胞存活。在FOXC1沉默的细胞中，抗凋亡蛋白Bcl-2水平降低，促凋亡蛋白Bax表达增加。进一步研究表明，FOXC1敲低可抑制PI3K/AKT/刺猬索尼信号通路/Gli2信号通路。过表达AKT或Gli2可逆转FOXC1沉默对A549细胞存活和凋亡的影响。综上所述，我们的结果表明，FOXC1沉默可降低癌细胞的存活率并促进其凋亡，且PI3K/AKT/刺猬索尼信号通路/Gli2信号通路在FOXC1沉默的作用中起重要作用。
