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表没食子儿茶素没食子酸酯抑制感染不同高危型人乳头瘤病毒亚型的宫颈癌细胞系的细胞生长并调节微小RNA表达。

Epigallocatechin gallate inhibits cell growth and regulates miRNA expression in cervical carcinoma cell lines infected with different high-risk human papillomavirus subtypes.

作者信息

Zhu Yu, Huang Yongfang, Liu Mingmin, Yan Qi, Zhao Wanhong, Yang Ping, Gao Qin, Wei Juanjuan, Zhao Wenxia, Ma Lishan

机构信息

Department of Obstetrics and Gynecology, Jiangwan Hospital, Shanghai 200434, P.R. China.

Department of Obstetrics and Gynecology, Yangpu Hospital Affiliated to Tongji University, Shanghai 200090, P.R. China.

出版信息

Exp Ther Med. 2019 Mar;17(3):1742-1748. doi: 10.3892/etm.2018.7131. Epub 2018 Dec 24.

Abstract

The aim of the present study was to investigate the inhibitory effects of the polyphenol epigallocatechin-3-gallate (EGCG) on the growth of cervical carcinoma cell lines infected with different high-risk human papillomavirus (HPV) subtypes, as well as the associated regulation of microRNA (miR) expression. Cell proliferation was measured using an MTT assay. The effects of 7 different concentrations of EGCG (100, 80, 60, 40, 20, 10 and 0 µg/ml) on HeLa cell proliferation were assessed. HeLa cell growth was significantly inhibited by EGCG in a dose- and time-dependent manner (P<0.05), and the IC was 90.74 and 72.74 µg/ml at 24 and 48 h, respectively. The expression of miR-210, miR-29a, miR-203 and miR-125b in HeLa (HPV16/18+), SiHa (HPV16+), CaSki (HPV16+) and C33A (HPV-) cell lines was measured using quantitative polymerase chain reaction analysis. In CA33 cells, miR-203 (all P<0.001) and miR-125b (P<0.01 and <0.0001) were significantly downregulated by EGCG, and miR-210 was significantly upregulated with 40 and 60 µg/ml EGCG (P<0.0001). miR-125b was significantly downregulated (P<0.001 and <0.0001), and miR-210 and miR-29 were significantly upregulated by ≤80 µg/ml EGCG in HeLa cells (all P<0.0001). In CaSki cells, miR-210, miR-29a (all P<0.001) and miR-125b (P<0.01-0.0001) were significantly upregulated by EGCG. In SiHa cells, miR-125b (both P<0.001) and miR-203 (P<0.01 and <0.0001) were significantly upregulated by EGCG. In conclusion, the results of the present study suggest that EGCG suppresses cervical carcinoma cell growth, possibly via regulating the expression of miRs, suggesting their potential as therapeutic targets for the control and prevention of cervical cancer. Additionally, EGCG may be considered a novel anti-cervical cancer drug in the future.

摘要

本研究的目的是调查多酚表没食子儿茶素-3-没食子酸酯(EGCG)对感染不同高危人乳头瘤病毒(HPV)亚型的宫颈癌细胞系生长的抑制作用,以及对微小RNA(miR)表达的相关调控。使用MTT法测量细胞增殖。评估了7种不同浓度(100、80、60、40、20、10和0µg/ml)的EGCG对HeLa细胞增殖的影响。EGCG以剂量和时间依赖性方式显著抑制HeLa细胞生长(P<0.05),在24小时和48小时时的半数抑制浓度(IC)分别为90.74和72.74µg/ml。使用定量聚合酶链反应分析测量HeLa(HPV16/18+)、SiHa(HPV16+)、CaSki(HPV16+)和C33A(HPV-)细胞系中miR-210、miR-29a、miR-203和miR-125b的表达。在C33A细胞中,EGCG显著下调miR-203(所有P<0.001)和miR-125b(P<0.01和<0.0001),40和60µg/ml的EGCG显著上调miR-210(P<0.0001)。在HeLa细胞中,≤80µg/ml的EGCG显著下调miR-125b(P<0.001和<0.0001),显著上调miR-210和miR-29(所有P<0.0001)。在CaSki细胞中,EGCG显著上调miR-210、miR-29a(所有P<0.001)和miR-125b(P<0.01 - 0.0001)。在SiHa细胞中,EGCG显著上调miR-125b(均P<0.001)和miR-203(P<0.01和<0.0001)。总之,本研究结果表明,EGCG可能通过调节miRs的表达来抑制宫颈癌细胞生长,提示它们作为控制和预防宫颈癌治疗靶点的潜力。此外,EGCG未来可能被视为一种新型抗宫颈癌药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78fe/6364235/e0b57974bba3/etm-17-03-1742-g00.jpg

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