Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9 expression in non-small-cell lung cancer by repressing nuclear factor-[kappa]B.

The liver X receptors (LXRs) is an important component of the nuclear receptor (NR) superfamily. Previous studies have shown that the LXRs possessed antitumor activity in various types of tumor cells. However, the complicated mechanisms underlying the antitumor activity remain largely unexplored. In this study, we incubated A549 cells with the compound T0901317, a specific LXRs agonist, for 24 h. The MTT assay was used to assess cell viability. Transwell assays were used to evaluate cell migration and invasion. The shRNA was utilized for RNA interference. The target gene and protein expression levels were assessed using reverse transcription-PCR and western blot assay. The DNA-binding activity of nuclear factor [kappa]B (NF-[kappa]B) was examined using electrophoretic mobility shift assays. Luciferase reporter assay was used to detect the binding of NF-[kappa]B to the matrix metalloproteinase-9 (MMP-9) promoter. We found that T0901317 inhibited the invasion and migration of A549 cells in a dose-dependent manner. Meanwhile, we further indicated that activation of LXR[beta], one subtype of LXRs, can downregulate MMP-9 expression. More importantly, activation of LXR[beta] triggered by T0901317 inhibited the invasion and metastasis of A549 cells by repressing NF-[kappa]B/MMP-9 signaling pathway. Taken together, our study shows that activation of LXRs triggered by T0901317 inhibits the invasion and metastasis of human non-small-cell lung cancer by repressing the NF-[kappa]B/MMP-9 signaling pathway. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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