Knockdown of T Cell Immunoglobulin and Mucin 1 (Tim-1) Suppresses Glioma Progression Through Inhibition of the Cytokine-PI3K/AKT Pathway.

Abstract

BackgroundGlioma 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.MethodsThe 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-β1, 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.ResultsTim-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-β1, 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.ConclusionTim-1 knockdown inhibited biological behaviors of glioma cells through the PI3K/AKT pathway, which may provide a novel therapy for glioma.