靶向 fascin 的小干扰 RNA 对人食管鳞癌细胞系的影响。

Effects of small interfering RNAs targeting fascin on human esophageal squamous cell carcinoma cell lines.

机构信息

Department of Pathology, Valencia University, Hospital General Universitario de Valencia, Avenida tres cruces N degrees 2, CP 46014, Valencia, Spain.

出版信息

Diagn Pathol. 2010 Jun 21;5:41. doi: 10.1186/1746-1596-5-41.

BACKGROUND

Fascin induces membrane protrusions and cell motility. Fascin overexpression was associated with poor prognosis, and its downregulation reduces cell motility and invasiveness in esophageal squamous cell carcinoma (ESCC). Using a stable knockdown cell line, we revealed the effect of fascin on cell growth, cell adhesion and tumor formation.

METHODS

We examined whether fascin is a potential target in ESCC using in vitro and in vivo studies utilizing a specific siRNA. We established a stable transfectant with downregulated fascin from KYSE170 cell line.

RESULTS

The fascin downregulated cell lines showed a slower growth pattern by 40.3% (p < 0.01) and detachment from collagen-coated plates by 53.6% (p < 0.01), compared to mock cells, suggesting that fascin plays a role in cell growth by maintaining cell adhesion to the extracellular matrix. In vivo, the tumor size was significantly smaller in the tumor with fascin knockdown cells than in mock cells by 95% at 30 days after inoculation.

CONCLUSIONS

These findings suggest that fascin overexpression plays a role in tumor growth and progression in ESCC and that cell death caused by its downregulation might be induced by cell adhesion loss. This indicates that targeting fascin pathway could be a novel therapeutic strategy for the human ESCC.

背景

Fascin 诱导细胞膜突起和细胞运动。 Fascin 的过表达与预后不良相关，其下调可降低食管鳞状细胞癌（ESCC）中的细胞运动性和侵袭性。通过使用稳定的敲低细胞系，我们揭示了 fascin 对细胞生长、细胞黏附和肿瘤形成的影响。

方法

我们使用特定的 siRNA 通过体外和体内研究来检查 fascin 是否是 ESCC 的潜在靶标。我们从 KYSE170 细胞系中建立了下调 fascin 的稳定转染细胞系。

结果

与 mock 细胞相比，下调 fascin 的细胞系的生长速度慢了 40.3%（p < 0.01），从胶原包被的平板上脱落的速度慢了 53.6%（p < 0.01），这表明 fascin 通过维持细胞与细胞外基质的黏附在细胞生长中发挥作用。在体内，接种后 30 天，fascin 敲低细胞的肿瘤大小比 mock 细胞小 95%。