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叉头框蛋白 A1 对宫颈癌增殖调控及 EMT 的影响。

Effects of forkhead Box protein A1 on cell proliferation regulating and EMT of cervical carcinoma.

机构信息

Department of Obstetrics, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7189-7196. doi: 10.26355/eurrev_201811_16252.

DOI:10.26355/eurrev_201811_16252
PMID:30468461
Abstract

OBJECTIVE

Cervical cancer is a common tumor in gynecological malignancies. However, the patients are often in an advanced stage when diagnosed. It was found that forkhead box protein A1 (FOXA1) is abnormally expressed in various tumors, such as breast cancer, ovarian cancer, and is closely related to tumorigenesis. This study aimed to investigate the expression and the related roles of FOXA1 in cervical cancer.

PATIENTS AND METHODS

Real Time-PCR (RT-PCR) and Western blot were used to analyze expression of FOXA1 in cervical cancer and adjacent tissue. The small-interfere RNA (siRNA) was adopted to down-regulate FOXA1 expression in HeLa cells. The effect of FOXA1 on apoptosis of HeLa cells was detected by using thiazolyl blue tetrazolium bromide (MTT) method. The apoptosis rate of HeLa cells was detected by using flow cytometry. The Western blot was selected to evaluate the epithelial mesenchymal transition (EMT) related protein, vimentin, E-cadherin, and vascular endothelial growth factor (VEGF) changes.

RESULTS

Compared with adjacent tissues, FOXA1 mRNA and protein expressions significantly increased in cervical cancer (p<0.05). SiRNA significantly reduced FOXA1 expression in Hela cells compared with the control group and siRNA-NC group, thus inhibiting tumor cell proliferation and enhancing cell apoptosis rate (p<0.05). E-cadherin elevated, Vimentin decreased, and VEGF reduced after FOXA1 siRNA treatment.

CONCLUSIONS

FOXA1 expression increased in cervical cancer. Inhibition of FOXA1 expression blocked the proliferation of cervical cancer, promoted tumor cell apoptosis, suppressed the occurrence of EMT and VEGF production, and can regulate cervical cancer metastasis. FOXA1 can be used as a new molecular biological target for cervical cancer diagnosis and treatment.

摘要

目的

宫颈癌是妇科恶性肿瘤中常见的肿瘤。然而,患者在诊断时往往处于晚期。研究发现叉头框蛋白 A1(FOXA1)在乳腺癌、卵巢癌等多种肿瘤中异常表达,与肿瘤的发生密切相关。本研究旨在探讨 FOXA1 在宫颈癌中的表达及其相关作用。

方法

采用实时荧光定量聚合酶链反应(RT-PCR)和 Western blot 分析 FOXA1 在宫颈癌及癌旁组织中的表达。采用小干扰 RNA(siRNA)下调 HeLa 细胞中 FOXA1 的表达。噻唑蓝溴化四唑(MTT)法检测 FOXA1 对 HeLa 细胞凋亡的影响。采用流式细胞术检测 HeLa 细胞的凋亡率。采用 Western blot 评价上皮间质转化(EMT)相关蛋白 vimentin、E-cadherin 和血管内皮生长因子(VEGF)的变化。

结果

与癌旁组织相比,宫颈癌中 FOXA1mRNA 和蛋白表达明显增加(p<0.05)。与对照组和 siRNA-NC 组相比,siRNA 显著降低了 HeLa 细胞中的 FOXA1 表达,从而抑制了肿瘤细胞的增殖,提高了细胞的凋亡率(p<0.05)。FOXA1siRNA 处理后 E-cadherin 升高,Vimentin 降低,VEGF 减少。

结论

FOXA1 在宫颈癌中表达增加。抑制 FOXA1 表达可阻断宫颈癌的增殖,促进肿瘤细胞凋亡,抑制 EMT 的发生和 VEGF 的产生,并能调节宫颈癌的转移。FOXA1 可作为宫颈癌诊断和治疗的新的分子生物学靶点。

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