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青蒿琥酯通过miR-142促进CD4+ T细胞向Th1分化,以增强卵巢癌细胞凋亡。

Artesunate promotes Th1 differentiation from CD4+ T cells to enhance cell apoptosis in ovarian cancer via miR-142.

作者信息

Chen Xiao, Zhang Xue-Ling, Zhang Guo-Hua, Gao Ying-Fang

机构信息

Department of Gynecology and Obstetrics, The Fourth Hospital of Shijiazhuang, Shijiazhuang, China.

出版信息

Braz J Med Biol Res. 2019;52(5):e7992. doi: 10.1590/1414-431X20197992. Epub 2019 Apr 29.

Abstract

The aim of this study was to evaluate the influence of artesunate on Th1 differentiation and its anti-tumor effect on ovarian cancer. A Murine ovarian cancer model was established by ID8 cells transplantation. The expression of miR-142 and Sirt1 proteins in peripheral CD4+ T cells were quantified with qRT-PCR and western blot, respectively. Peripheral CD4+ T cells were induced for Th1 differentiation. The percentages of apoptosis of Th1/CD4+ T cells and ovarian cancer cells were analyzed by flow cytometry. The IFN-γ level was examined through enzyme-linked immunosorbent assay. Artesunate promoted miR-142 expression in peripheral CD4+ T cells and Th1 differentiation from CD4+ T cells. Artesunate promoted cell apoptosis of ovarian cancer cells by inducing Th1 differentiation. By up-regulating miR-142, artesunate suppressed Sirt1 level and promoted Th1 differentiation. Artesunate enhanced the pro-apoptotic effects of Th1 cells on ovarian cancer via the miR-142/Sirt1 pathway. Artesunate promoted Th1 differentiation from CD4+ T cells by down-regulating Sirt1 through miR-142, thereby enhancing cell apoptosis in ovarian cancer.

摘要

本研究旨在评估青蒿琥酯对Th1分化的影响及其对卵巢癌的抗肿瘤作用。通过ID8细胞移植建立小鼠卵巢癌模型。分别采用qRT-PCR和蛋白质免疫印迹法对外周血CD4+ T细胞中miR-142和Sirt1蛋白的表达进行定量分析。诱导外周血CD4+ T细胞向Th1分化。采用流式细胞术分析Th1/CD4+ T细胞和卵巢癌细胞的凋亡百分比。通过酶联免疫吸附测定法检测IFN-γ水平。青蒿琥酯促进外周血CD4+ T细胞中miR-142的表达以及CD4+ T细胞向Th1分化。青蒿琥酯通过诱导Th1分化促进卵巢癌细胞凋亡。通过上调miR-142,青蒿琥酯抑制Sirt1水平并促进Th1分化。青蒿琥酯通过miR-142/Sirt1途径增强Th1细胞对卵巢癌的促凋亡作用。青蒿琥酯通过miR-142下调Sirt1,促进CD4+ T细胞向Th1分化,从而增强卵巢癌细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e6ef/6489539/71438d52d6d1/1414-431X-bjmbr-52-5-e7992-gf001.jpg

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