Objective: To investigate the roles of inflammatory factors and nuclear factor kappa B (NF-kappaB) signal pathway in metastasis of oral squamous cell carcinoma.
Methods: The oral squamous cell carcinoma cell lines with highly metastasis potential (Tb) and lower metastasis potential (Tca8113) were used in this study. The levels of NF-kappaB activity in oral squamous cell carcinoma cell lines were determined by Western blotting and luciferase reporter assay. pBalphabe-IkappaBalpha-SR expression vector or NF-kappaB inhibitor pyrolidinedithiocarbamate (PDTC) was used to inhibit NF-kappaB, and cell migration was examined by transwell assay. The secretion of tumor necrosis factor-alpha (TNF-alpha), IL-1alpha, IL-6, IL-8 and GM-CSF proinflammatory cytokines was determined by ELISA when Tb cells were transfected with pBalphabe-SR-IkappaBalpha or treated with PDTC.
Results: Western blotting showed that the levels of phosphorIkappaBalpha and phosphor-p65 were highly expressed in Tb cells. Tb cells had high level of constitutive NF-kappaB activity and were more sensitive to TNF-alpha. The migration of highly metastatic Tb cells, either transfected with dominant-negative mutant inhibitor pBalphabe-SR-IkappaBalpha or treated with PDTC, was suppressed when determined by transwell assay. The secretion of proinflammatory cytokines, including TNF-alpha, IL-1alpha, IL-6, IL-8 and granulocyte-macrophage colony stimulating factor (GM-CSF), was inhibited by pBalphabe-SR-IkappaBalpha transfection or PDTC treatment.
Conclusions: The inflammatory factors such as TNF-alpha could promote oral squamous cell carcinoma cell metastasis via NF-kappaB signal pathway.