Icotinib inhibits the invasion of Tca8113 cells via downregulation of nuclear factor κB-mediated matrix metalloproteinase expression

Abstract

Icotinib is an epidermal growth factor receptor tyrosine kinase inhibitor, which has been revealed to inhibit proliferation in tumor cells. However, the effect of icotinib on cancer cell metastasis remains to be explained. This study examines the effect of icotinib on the migration and invasion of squamous cells of tongue carcinoma (Tca8113 cells) in vitro. The results of the Boyden chamber invasion assay demonstrated that icotinib reduced cell invasion, suppressed the protein levels of matrix metalloproteinases (MMPs), MMP-2 and MMP-9, and increased the expression of tissue inhibitor of metalloproteinase-1. In addition, icotinib was found to significantly decrease the protein levels of nuclear factor κB (NF-κB) p65, which suggested that icotinib inhibits NF-κB activity. Furthermore, treatment with the NF-κB inhibitor, pyrrolidine dithiocarbamate, suppressed cell invasion and MMP-2 expression. These results suggested that icotinib inhibits the invasion of Tca8113 cells by downregulating MMP via the inactivation of the NF-κB signaling pathways.

IRX5 promotes NF‐κB signalling to increase proliferation, migration and invasion via OPN in tongue squamous cell carcinoma

“…These results confirmed that IRX5 activated the NF‐κB pathway by targeting OPN promoter. MMP2 acts as downstream of NF‐κB in cancers, where it degrades the ECM, which is a pivotal step in tumour metastasis and invasion . In our study, MMP2 was up‐regulated by IRX5/OPN signalling, which partially explains the promoting effect of IRX5 in TSCC.…”

“…Our results indicated that IRX5 overexpression resulted in increased nuclear p65 level and led to increased IκBα degradation. Furthermore, levels of MMP2, which acts as the downstream of the NF‐κB pathway, were also elevated in IRX5 overexpressing cells. Consistent with these results, the knockdown of IRX5 expression using shRNA resulted in decreased nuclear p65, MMP2 expression and IκBα degradation (Figure A).…”

Nuclear Factor Kappa B, Matrix Metalloproteinase-1, p53, and Ki-67 Expressions in the Primary Tumors and the Lymph Node Metastases of Colorectal Cancer Cases

“…In fact, in the present study, the MMP-1 expression was nonsignificantly decreased in the metastatic lymph nodes. There have been several studies associating NF- κ B with MMPs suggesting that migratory genes may support NF- κ B in inflammation and carcinogenesis [ 23 , 24 , 34 ]. Considering that NF- κ B triggers many extracellular events like tumor angiogenesis, it is very likely to have a relation with MMP-1.…”

Mechanisms of Invasion in Head and Neck Cancer

“…Radiation has been found to induce migration and invasion, 285 and treatment with invasion inhibitors during radiation therapy could potentially enhance its efficacy. 286,287 Inhibitors targeting EGFR, 288 Na 275 Src, 91 and microtubules 289 can inhibit invasion at concentrations that are not toxic to cells and could be useful in counteracting radiation-induced spread. …”