Downregulations of AKT/mTOR Signaling Pathway for Salmonella-Mediated Suppression of Matrix Metalloproteinases-9 Expression in Mouse Tumor Models

AKT/mTOR 信号通路下调导致小鼠肿瘤模型中沙门氏菌介导的基质金属蛋白酶-9 表达抑制

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作者:Yu-Tzu Tsao, Chun-Yu Kuo, Shun-Ping Cheng, Che-Hsin Lee

Abstract

The roles of Matrix MetalloProteinases (MMPs), such as MMP-9, in tumor metastasis are well studied, and this in turns stimulates the development of MMP inhibitors as antitumor agents. Previously, Salmonella accumulation was observed in the metastatic nodules of the lungs after systemic administration. Salmonella significantly enhanced the survival of the pulmonary metastatic tumor-bearing mice. Based on our previous observation, we hypothesized that Salmonella could affect metastasis-related protein expression. The treatment of Salmonella clearly reduced the expression of MMP-9. Meanwhile, the MMP-9 related signaling pathways, including Phosph-Protein Kinase B (P-AKT) and Phosph-mammalian Targets Of Rapamycin (P-mTOR) were decreased after a Salmonella treatment. The Salmonella inhibited tumor cell migration by wound-healing and Transwell assay. The anti-metastatic effects of Salmonella were evaluated in mice bearing experimental metastasis tumor models. Consequently, Salmonella inhibited the expression of MMP-9 by reducing the AKT/mTOR pathway and metastatic nodules in vivo.

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