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人乳头瘤病毒11型(HPV11)感染细胞模型的完整性及(-)-表没食子儿茶素-3-没食子酸酯作为潜在HPV11抑制剂的鉴定。

Integrity of a HPV11 infection cell model and identification of (-)-Epigallocatechin-3-gallate as a potential HPV11 inhibitor.

作者信息

Sun Yang, Li Xinyu, Song Shasha, Wang Yongfang, Gu Heng

机构信息

Institute of Dermatology, Chinese Academy of Medical Science and Peking Union Medical College, Nanjing, China.

出版信息

Oncotarget. 2016 Jun 14;7(24):37092-37102. doi: 10.18632/oncotarget.9249.

Abstract

BACKGROUND

Condyloma acuminatum (CA) is one of the most common sexually transmitted diseases and induced by low-risk human papillomaviruses (HPVs), mainly HPV type 6 and 11. Here, we report the identification of (-)-Epigallocatechin-3-gallate (EGCG) by an HPV11 infection cell model.

RESULTS

The recombined HPV11.HaCaT cells had stable HPV 11 early genes expression. The introducing of HPV11 genome significantly increased the proliferation of HPV11.HaCaT cells, as well as the proportion of cells in S and G2/M phases. After treated with rhIFN-α 2a, IFN signaling pathway was activated in both HaCaT and HPV11.HaCaT cells, while HPV11 decreased the activation level. In addition, rhIFN-α 2a, could inhibit expression of HPV 11 E6 and E7 mRNA significantly (P<0.05). However, cell growth and cell cycle did not show statistical difference (P>0.05). Nevertheless, EGCG, a major active constituent in tea polyphenol, showed strong anti-HPV11 effect, which inhibited HPV11 E6 and E7 mRNA.

METHODS

Gene transfection technique was used to introduce HPV11 genome into HaCaT cells, named HPV11.HaCaT cells. With the established cell model, we explore the anti-HPV11 effect of (-)-Epigallocatechin-3-gallate (EGCG) on cell growth, viability and affection on expression HPV11 E6 and E7 mRNA.

CONCLUSIONS

Our data collectively demonstrated that the recombinant HPV11.HaCaT cells were integral and practical to be a cell model to test anti-HPV11 agents and explore the interaction between HPV11 genes and host cells. And EGCG inhibits expression of HPV11 E6 and E7 mRNA in the recombinant HPV11.HaCaT cells.

摘要

背景

尖锐湿疣(CA)是最常见的性传播疾病之一,由低危型人乳头瘤病毒(HPV)引起,主要是6型和11型HPV。在此,我们报告通过HPV11感染细胞模型鉴定出(-)-表没食子儿茶素-3-没食子酸酯(EGCG)。

结果

重组HPV11.HaCaT细胞具有稳定的HPV 11早期基因表达。HPV11基因组的导入显著增加了HPV11.HaCaT细胞的增殖,以及S期和G2/M期细胞的比例。用重组人干扰素α 2a(rhIFN-α 2a)处理后,HaCaT细胞和HPV11.HaCaT细胞中的IFN信号通路均被激活,而HPV11降低了激活水平。此外,rhIFN-α 2a可显著抑制HPV 11 E6和E7 mRNA的表达(P<0.05)。然而,细胞生长和细胞周期未显示出统计学差异(P>0.05)。尽管如此,EGCG作为茶多酚中的主要活性成分,显示出强大的抗HPV11作用,可抑制HPV11 E6和E7 mRNA。

方法

采用基因转染技术将HPV11基因组导入HaCaT细胞,命名为HPV11.HaCaT细胞。利用建立的细胞模型,我们探讨了(-)-表没食子儿茶素-3-没食子酸酯(EGCG)对细胞生长、活力的抗HPV11作用以及对HPV11 E6和E7 mRNA表达的影响。

结论

我们的数据共同表明,重组HPV11.HaCaT细胞作为测试抗HPV11药物和探索HPV11基因与宿主细胞之间相互作用的细胞模型是完整且实用的。并且EGCG可抑制重组HPV11.HaCaT细胞中HPV11 E6和E7 mRNA的表达。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9b2e/5095061/1f9474eb9e6b/oncotarget-07-37092-g001.jpg

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