TLR4/NF-κB表达升高促进宫颈癌增殖和转移的作用及机制

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英文篇名：Effect and mechanism of TLR4/NF-κB signaling pathway on proliferation and metastasis of cervical cancer 作者：蔡静 ; 张丹 ; 张燕 英文作者：CAI Jing;ZHANG Dan;ZHANG Yan;The department of Obstetrics and Gynecology,Wuhan Children's Hospital (Wuhan Maternal and Child Healthcare Hospital),Tongji Medical College,Huazhong University of Science & Technology; 关键词：TLR4 ; NF-κB ; 宫颈癌 ; 侵袭 ; 迁移 ; 增殖 ; 病理分级 英文关键词：TLR4;;NF-κB;;cervical cancer;;invasion;;migration;;proliferation;;pathological grading 中文刊名：SYJK 英文刊名：Chinese Journal of Reproductive Health 机构：华中科技大学同济医学院附属武汉儿童医院(武汉市妇幼保健院)妇产科;武汉大学人民医院妇产科; 出版日期：2019-01-11 出版单位：中国生育健康杂志 年：2019 期：v.30 基金：湖北省卫生计生委重点支撑项目(WJ2017Z002) 语种：中文; 页：SYJK201901005 页数：5 CN：01 ISSN：11-4831/R 分类号：25-29

摘要

目的研究Toll样受体4(Toll-like Receptor 4,TLR-4)/核因子-κB(nuclear factor-kappa B,NF-κB)分子在宫颈癌中的表达,探讨TLR4/NF-κB表达与宫颈癌增殖、迁移的关系及具体机制。方法采用实时定量PCR(quantitative real-time PCR,qRT-PCR)比较宫颈癌组织及癌旁组织中TLR4/NF-κB的表达。采用脂质体介导转染方法,根据人宫颈癌细胞株HCE1细胞TLR4表达情况,分为Blank、阴性对照、TLR4沉默、TLR4过表达4组。采用CCK8、划痕实验、Transwell实验检测TLR4对细胞增殖、迁移、侵袭,并进一步检测Myd88,ERK1/2及NF-κB信号分子改变。结果肿瘤组织TLR4/NF-κB的表达显著高于癌旁组织(P <0. 05);宫颈癌细胞株HCE1中TLR4/NF-κB表达显著高于正常宫颈上皮细胞(P <0. 05)。TLR4沉默组细胞增殖能力较NC组显著下降(P <0. 05),过表达TLR4细胞增殖能力显著升高(P <0. 05)。TLR4沉默组愈合面积比例显著低于NC组(P <0. 05),过表达TLR4组愈合面积比例显著升高(P <0. 05)。TLR4沉默组穿膜细胞数明显少于NC组(P <0. 05),过表达TLR4组穿膜细胞数明显多于NC组(P <0. 05)。TLR4沉默组Myd88,ERK1/2及NF-κB的表达显著低于NC组; TLR4过表达组Myd88,ERK1/2及NF-κB的蛋白表达显著高于NC组(P均<0. 05)。结论TLR4/NF-κB在宫颈癌中表达升高,促进宫颈癌细胞增殖、迁移、侵袭。
        Objective To study the expression of Toll-like Receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) in cervical cancer,and to explore the relationship between TLR4/NF-κB expression with proliferation and migration of cervical cancer and its mechanism. Methods Real time quantitative PCR was used to compare the expression of TLR4/NF-κB in cervical cancer tissues and adjacent tissues. The expression of TLR4 in human cervical cancer cell line HCE1 was silenced or over-expressed by liposome-mediated transfection. The effect of TLR4 on cell proliferation,migration,invasiveness ability was detected by CCK8,scratch test and Transwell assay. The changes of Myd88,ERK1/2 and NF-κB signal molecules were further detected. Results The expression of TLR4/NF-κB in tumor tissue was significantly higher than that of adjacent tissue (P <0. 05),and the relative expression of TLR4/NF-κB in HCE1 was significantly higher than that of normal cervical epithelial cells (P <0. 05). The cell proliferation ability of TLR4 silencing group was significantly lower than that of NC group (P < 0. 05),while the ability in TLR4 overexpressed cells was significantly higher (P < 0. 05). The proportion of healing area in TLR4 silencing group was significantly lower than that in NC group (P < 0. 05),while the proportion in TLR4 overexpressed group was significantly increased (P < 0. 05). The number of penetrating cells in TLR4 silencing group was significantly less than that in group NC (P < 0. 05),while the number in TLR4 overexpressed group was significantly higher (P < 0. 05). The expression of Myd88,ERK1/2 and NF-κB in TLR4 silencing group was significantly lower than that in NC group,while their expression in TLR4 overexpressed group was significantly higher (P < 0. 05). Conclusion Upregulated TLR4/NF-κB activation could promote the proliferation,migration and invasion of cervical cancer.

引文

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