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IL-8 的过表达通过 PI3K-Akt 信号通路和 EMT 促进三阴性乳腺癌中的细胞迁移。

Overexpression of IL-8 promotes cell migration via PI3K-Akt signaling pathway and EMT in triple-negative breast cancer.

机构信息

Key Laboratory of Diagnostic Medicine Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, PR China; Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, PR China.

Department of Laboratory Medicine, Chongqing Medical University, 1 Yixueyuan Road, Yuzhong, Chongqing, 400016, PR China.

出版信息

Pathol Res Pract. 2020 Apr;216(4):152902. doi: 10.1016/j.prp.2020.152902. Epub 2020 Feb 26.

DOI:10.1016/j.prp.2020.152902
PMID:32147274
Abstract

Triple-negative breast cancer (TNBC) is a type of malignant and heterogeneous tumor in premenopausal females with ineffective therapeutic targets. IL-8 is one of the earliest discovered chemotaxis cytokines which expression is closely related to the progress of various cancers. Previous studies showed that IL-8 determines the prognosis of TNBC patients, nevertheless how IL-8 influences the progress of TNBC is unclear. In our studies, we discovered that overexpression of IL-8 promotes TNBC cells (TNBCs) migration and tumor growth via the PI3K-Akt and MAPK signaling pathway. Cell-cycle of TNBCs arrest at S phase by overexpression of IL-8, however, there is no significant variation on the cell viability and cell apoptosis of TNBCs. Besides, overexpression of IL-8 result in the downregulation of E-cadherin and the upregulation of Cyclin B1 in MDA-MB-231 cells. Taken together, our results suggest that IL-8 performs a crucial role in the progress of TNBC, and it could be a novel therapeutic target of TNBC.

摘要

三阴性乳腺癌(TNBC)是一种在绝经前女性中恶性且异质性的肿瘤,缺乏有效的治疗靶点。IL-8 是最早发现的趋化因子之一,其表达与各种癌症的进展密切相关。先前的研究表明,IL-8 决定了 TNBC 患者的预后,然而,IL-8 如何影响 TNBC 的进展尚不清楚。在我们的研究中,我们发现过表达 IL-8 通过 PI3K-Akt 和 MAPK 信号通路促进 TNBC 细胞(TNBCs)迁移和肿瘤生长。IL-8 的过表达使 TNBCs 的细胞周期停滞在 S 期,但对 TNBCs 的细胞活力和细胞凋亡没有显著影响。此外,过表达 IL-8 导致 MDA-MB-231 细胞中 E-钙黏蛋白下调和 Cyclin B1 上调。综上所述,我们的结果表明,IL-8 在 TNBC 的进展中起着关键作用,它可能是 TNBC 的一个新的治疗靶点。

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