The voltage-gated sodium channel Nav1.7 associated with endometrial cancer

The voltage-gated sodium channel Nav1.7 associated with endometrial cancer
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电压门控钠通道 Nav1.7 与子宫内膜癌相关

DOI:
10.7150/jca.31544
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发表时间:
2019-08
期刊:
影响因子:
3.9
通讯作者:
Liang Hong
Liang Hong
中科院分区:
医学3区
文献类型:
--
作者:
Junxiu Liu;Hao Tan;Wancai Yang;Shuzhong Yao;Liang Hong

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背景:子宫内膜癌是发达国家妇女最常见的妇科恶性肿瘤。尽管最近在多种癌症中电压门控钠通道(Nav)的功能表征方面取得了进展,但对Nav在人类子宫内膜癌中的表达知之甚少。本研究旨在确定Nav的作用和该通道在子宫内膜癌中的分子性质。方法:采用PCR方法检测子宫内膜癌组织中Nav亚基的表达水平。使用药理学试剂来研究子宫内膜癌细胞中的Nav功能。流式细胞术检测肿瘤细胞凋亡,侵袭实验检测肿瘤转移。结果如下:应用真实的时间PCR检测子宫内膜癌组织及癌旁组织中Nav α、β亚基的转录水平,Nav 1. 7在子宫内膜癌组织中表达最高。Nav1.7水平与肿瘤大小、局部淋巴结转移、5年和10年生存率密切相关。通过Nav1.7阻断剂PF-05089771抑制该通道,促进癌细胞凋亡并减弱癌细胞侵袭。结论:这些结果建立了电压门控钠通道蛋白与子宫内膜癌之间的关系,并表明Nav1.7是一种潜在的预后生物标志物,可作为子宫内膜癌的新治疗靶点。
Background: Endometrial cancer is the most common gynecologic malignancy in women in the developed countries. Despite recent progress in functional characterization of voltage-gated sodium channel (Nav) in multiple cancers, very little was known about the expression of Nav in human endometrial cancer. The present study sought to determine the role of Nav and molecular nature of this channel in the endometrial cancer. Methods: PCR approach was introduced to determine expression level of Nav subunits in endometrial cancer specimens. Pharmacological agents were used to investigate Nav function in endometrial cancer cells. Flow cytometry were used to test cancer apoptosis, and invasion assays were applied to test tumor metastasis. Results: Transcriptional levels of the all Nav α and β subunits were determined by real time-PCR in endometrial cancer with pair tissues of carcinoma and adjacent nonneoplastic tissue, Nav1.7 was the most highly expressed Nav subtype in endometrial cancer tissues. Nav1.7 level was closely associated with tumor size, local lymph node metastasis, and 5-year and 10-year survival ratio. Inhibition of this channel by Nav1.7 blocker PF-05089771, promoted cancer apoptosis and attenuated cancer cell invasion. Conclusion: These results establish a relationship between voltage-gated sodium channel protein and endometrial cancer, and suggest that Nav1.7 is a potential prognostic biomarker and could serve as a novel therapeutic target for endometrial cancer.
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