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结肠癌诱导的白细胞介素-35抑制β-连环蛋白介导的促癌活性。

Colon cancer-induced interleukin-35 inhibits beta-catenin-mediated pro-oncogenic activity.

作者信息

Jiang Yueqiang, Ma Yanling, Li RuiChao, Sun JianHai

机构信息

Department of Gerontology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, China.

Department of Oncology, the Third People's Hospital, Wuhan, Hubei Province, China.

出版信息

Oncotarget. 2017 Dec 1;9(15):11989-11998. doi: 10.18632/oncotarget.22857. eCollection 2018 Feb 23.

Abstract

The occurrence and development of colon cancer is closely related to inflammation. Therefore, this study was conducted a current retrospective research to study the effect of IL-35 (interleukin 35), a newly identified anti-infective factor, on colon cancer development. The expression of IL-35 in colon cancer samples and their adjacent normal mucosa by real-time PCR, ELISA (enzyme-linked immunosorbent assay). The effect of IL-35 on patient survival, colon cancer progression, and its effect on Wnt/β-catenine signaling pathway was also assessed. IL-35 is minimally expressed in colon cancer tissues but is highly expressed in adjacent normal tissues. The down-regulation of IL-35 was significantly associated with the American Cancer Joint Committee stage and overall survival of colon cancer patients. The overexpression of IL-35 in colon cancer cells inhibits cell migration, invasion, proliferation, colony formation and cancer stem cells by inhibiting beta-catenin. IL-35 inhibits colon neoplasms in mouse. Our results suggest that IL-35 has an inhibitory effect on the development of colon cancer as a novel prognostic indicator and potential therapeutic target.

摘要

结肠癌的发生与发展与炎症密切相关。因此,本研究进行了一项回顾性研究,以探讨新发现的抗感染因子白细胞介素35(IL-35)对结肠癌发展的影响。通过实时荧光定量PCR、酶联免疫吸附测定(ELISA)检测结肠癌样本及其相邻正常黏膜中IL-35的表达。还评估了IL-35对患者生存、结肠癌进展的影响及其对Wnt/β-连环蛋白信号通路的作用。IL-35在结肠癌组织中表达极低,但在相邻正常组织中高表达。IL-35的下调与美国癌症联合委员会分期及结肠癌患者的总生存期显著相关。在结肠癌细胞中过表达IL-35可通过抑制β-连环蛋白来抑制细胞迁移、侵袭、增殖、集落形成及癌症干细胞。IL-35可抑制小鼠结肠癌的发生。我们的研究结果表明,IL-35作为一种新的预后指标和潜在治疗靶点,对结肠癌的发展具有抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b608/5844723/42cc46e9d784/oncotarget-09-11989-g001.jpg

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