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T 细胞免疫球蛋白和粘蛋白 1(Tim-1)的敲低可通过抑制细胞因子-PI3K/AKT 信号通路来遏制胶质瘤进展
Authors Zhou P, Fei M, Han Y, Zhou M, Wang H
Received 19 April 2020
Accepted for publication 13 July 2020
Published 4 August 2020 Volume 2020:13 Pages 7433—7445
DOI https://doi.org/10.2147/OTT.S255117
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Nicola Silvestris
Background: Glioma is formed by abnormal proliferation of glial cells in the brain. T cell immunoglobulin and mucin 1 (Tim-1) is linked to cancer development. This study aimed to assess Tim-1 functions in biological behaviors.
Methods: The glioma tissues and paracancerous tissues were collected. The pathological morphology of glioma and positive expression of Tim-1 were evaluated. The sh-Tim-1 lentivirus vector was infected into U251 and U87 cells to evaluate glioma cell malignant behaviors. The differentially expressed terms in glioma cells were analyzed by Agilent microarray analysis, and enrichment analyses were performed. Levels of cytokines (TGF-β 1, IL-6, IL-4 and IL-10) and the PI3K/AKT pathway were measured. U87 cells with sh-Tim-1 were transplanted into nude mice, and the volume and weight of tumors were measured.
Results: Tim-1 levels in glioma tissues and cells were higher than those in glial tissues and cells. Tim-1 knockdown prevented glioma cell proliferation, invasion and migration, and reduced TGF-β 1, IL-6, IL-4 and IL-10 levels of glioma. Co-treatment of PI3K/AKT pathway activator and knockdown Tim-1 partially reversed these outcomes. After Tim-1 knockdown, tumor volume and weight and Ki67-positive rate of nude mice were diminished.
Conclusion: Tim-1 knockdown inhibited biological behaviors of glioma cells through the PI3K/AKT pathway, which may provide a novel therapy for glioma.
Keywords: glioma, Tim-1, PI3K/AKT pathway, proliferation, tumor xenografts