Evodiamine inactivates NF-κB and potentiates the antitumor effects of gemcitabine on tongue cancer both in vitro and in vivo

Objective: The aim of this study was to investigate whether evodiamine (EVO) could potentiate the antitumor activity of gemcitabine (GEM) in tongue cancer cells and determine its potential underlying mechanisms. Materials and methods: Human Tca8113 and CAL-27 tongue squamous carcinoma cell lines were treated with EVO and GEM in different sequences and doses, after which cell proliferation was measured. Drug interactions were analyzed using the Chou-Talalay method with CompuSyn software. Clonality, apoptosis, and migration were measured using the plate clone formation assay, annexin V/propidium iodide (PI) staining, Hoechst 33342 staining, and the wound-healing test. The activity of the nuclear factor kappa light-chain enhancer of activated B cell (NF-kappa B) p65 subunit and its downstream proteins was quantified by Western blotting. The effects of the drug combination in vivo were assessed using a CAL-27 heterotopic xenograft model. Results: EVO and GEM had synergistic effects on CAL-27 and Tca8113 cell lines in time- and concentration-dependent manners. Combination of drugs inhibited cell proliferation and migration and reduced the expression of NF-kappa B p65, B cell lymphoma 2 (Bcl-2), and B cell lymphoma extra large (Bcl-xl) compared with the control and either drug alone. In vivo, combination treatment of the xenograft model with EVO and GEM led to a significant reduction in tumor volume growth and inhibited the activation of NF-kappa B p65 with no obvious adverse reactions. Conclusion: The results of this study showed that EVO may inhibit cancer cells by suppressing NF-kappa B activity, and in combination with GEM, it may increase the chemosensitivity of tongue squamous cancer cells, thereby improving the treatment response.