下调转录抑制因子 ZEB1 对卵巢癌细胞上皮-间充质转化的影响。

Effect of down-regulated transcriptional repressor ZEB1 on the epithelial-mesenchymal transition of ovarian cancer cells.

机构信息

*Department of Pathogenic Biology and Immunology of Medical College, Southeast University, Nanjing, China; †Department of Microbiology, Bengbu Medical School, Bengbu, PR China; and ‡Department of Gynecology and Obstetrics, Zhongda Hospital, Medical School, Southeast University, Nanjing, PR China.

出版信息

Int J Gynecol Cancer. 2013 Oct;23(8):1357-66. doi: 10.1097/IGC.0b013e3182a5e760.

DOI:10.1097/IGC.0b013e3182a5e760

PMID:24257549

Abstract

BACKGROUND

Progress has been made against early events of malignant transformation and drug resistance associated with epithelial ovarian cancer; uncontrolled metastases, however, still accounts for most patient deaths. The molecular mechanism that regulates the process of epithelial ovarian cancer metastases is not yet clearly understood. The purpose of this study was to investigate the effect of down-regulating the transcriptional repressor zinc-finger E-box-binding homeobox 1 (ZEB1) on an epithelial-mesenchymal transition (EMT) of human ovarian cancer SKOV3 cell line in vitro and in vivo.

METHODS

The human ovarian cancer cells SKOV3 and HO8910 were transfected with an expression vector-based small hairpin RNA (shRNA) targeting ZEB1 (shZEB1), and the stably transfected cells were selected. Colony-forming, wound-healing, and cellular migration assays were respectively used. The tumorigenicity of shZEB1-SKOV3 was also evaluated in mice.

RESULTS

The shZEB1-SKOV3 and shZEB1-HO8910 cells showed a lower level of ZEB1 expression and weaker cell migration than the control cells. Moreover, down-regulating ZEB1 expression with shRNA in the cells enhanced the expression of miR-200c that acted as a tumor suppressor to inhibit the epithelial-mesenchymal transition of shZEB1-SKOV3 cells and to block shZEB1-SKOV3 cell metastasis in vivo. The shRNA-mediated down-regulation ZEB1 in SKOV3 cells significantly decreased the tumor growth in the xenograft mice.

CONCLUSION

The shZEB1-mediated down-regulation of the ZEB1 expression in the SKOV3 cells may be considered for future clinical trials.

摘要

背景

在与上皮性卵巢癌相关的早期恶性转化和耐药事件方面已经取得了进展；然而，不受控制的转移仍然是大多数患者死亡的原因。调节上皮性卵巢癌转移过程的分子机制尚不清楚。本研究旨在探讨下调转录抑制因子锌指 E 盒结合同源盒 1（ZEB1）在上皮-间质转化（EMT）过程中对人卵巢癌细胞 SKOV3 系体外和体内的影响。

方法

用人卵巢癌细胞 SKOV3 和 HO8910 转染靶向 ZEB1 的表达载体短发夹 RNA（shRNA）（shZEB1），并选择稳定转染的细胞。分别进行集落形成、划痕愈合和细胞迁移实验。还评估了 shZEB1-SKOV3 在小鼠中的致瘤性。

结果

shZEB1-SKOV3 和 shZEB1-HO8910 细胞的 ZEB1 表达水平较低，细胞迁移能力较弱。此外，shRNA 下调细胞中的 ZEB1 表达增强了 miR-200c 的表达，miR-200c 作为一种肿瘤抑制因子抑制 shZEB1-SKOV3 细胞的上皮-间质转化，并阻断 shZEB1-SKOV3 细胞在体内的转移。shRNA 介导的 SKOV3 细胞中 ZEB1 的下调显著降低了异种移植小鼠中的肿瘤生长。