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单纯疱疹病毒进入介体通过 STAT5/Foxp3 信号通路调节卵巢癌细胞中 Tregs 的转导。

Herpesvirus entry mediator regulates the transduction of Tregs via STAT5/Foxp3 signaling pathway in ovarian cancer cells.

机构信息

Department of Obstetrics and Gynecology.

Department of Pathology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, China.

出版信息

Anticancer Drugs. 2023 Jan 1;34(1):73-80. doi: 10.1097/CAD.0000000000001336. Epub 2022 Aug 9.

Abstract

The ratio of regulatory T cells (Treg) in peripheral blood of cancer patients has a closely correlation to the occurrence and development of ovarian cancer. In this study, our aim to explore the expression of herpesvirus entry mediator (HVEM) in ovarian cancer and its correlation with Tregs. The expression of HVEM in peripheral blood of ovarian cancer patients was detected by ELISA, and the ratio of CD4+ CD25 + Foxp3 positive Tregs cells was detected by flow cytometry. Ovarian cancer cell lines with high- and low-HVEM expression were constructed. CD4+ cells were co-cultured with ovarian cancer (OC) cells, and the expressions of IL-2 and TGF-β1 in the supernatant of cells were detected by ELISA, and western blot was used to detect the expressions of STAT5, p-STAT5, and Foxp3. The results indicated that the number of Treg cells in the peripheral blood of OC patients increased, and the expression of HVEM increased, the two have a certain correlation. At the same time, the overexpression of HVEM promoted the expression of cytokines IL-2 and TGF- β1, promoted the activation of STAT5 and the expression of Foxp3, leading to an increase in the positive rate of Treg, while the HVEM gene silence group was just the opposite. Our results showed that the expression of HVEM in OC cells has a positive regulation effect on Tregs through the STAT5/Foxp3 signaling pathway. To provide experimental basis and related mechanism for the clinical treatment of ovarian cancer.

摘要

肿瘤患者外周血调节性 T 细胞(Treg)的比例与卵巢癌的发生发展密切相关。本研究旨在探讨疱疹病毒进入介体(HVEM)在卵巢癌中的表达及其与 Tregs 的相关性。采用 ELISA 法检测卵巢癌患者外周血中 HVEM 的表达,采用流式细胞术检测 CD4+CD25+Foxp3 阳性 Tregs 细胞的比例。构建高表达和低表达 HVEM 的卵巢癌细胞系。将 CD4+细胞与卵巢癌细胞(OC)共培养,采用 ELISA 法检测细胞上清液中 IL-2 和 TGF-β1 的表达,采用 Western blot 法检测 STAT5、p-STAT5 和 Foxp3 的表达。结果表明,OC 患者外周血 Treg 细胞数量增加,HVEM 表达增加,两者具有一定的相关性。同时,HVEM 的过表达促进了细胞因子 IL-2 和 TGF-β1 的表达,促进了 STAT5 的激活和 Foxp3 的表达,导致 Treg 的阳性率增加,而 HVEM 基因沉默组则恰恰相反。我们的结果表明,OC 细胞中 HVEM 的表达通过 STAT5/Foxp3 信号通路对 Tregs 具有正向调节作用。为卵巢癌的临床治疗提供实验依据和相关机制。

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