Baicalein Exerts Anti-Tumor Effects on Nasopharyngeal Carcinoma by Mediating the FOXO-1/NF-κB Signaling Pathway

Abstract

Background: Nasopharyngeal carcinoma (NPC) is a highly malignant head and neck tumor, with most patients having lymph node metastasis at the time of diagnosis. Studies have shown that forkhead box protein O-1 (FOXO-1) and nuclear factor kappa-B (NF-κB) are associated with resistance to radiotherapy and chemotherapy in NPC. Baicalein can play an anti-inflammatory role by negatively regulating the activation of NF-κB and FOXO. The aim of this study was to investigate the effect of baicalein on the FOXO-1/NF-κB pathway in NPC. Methods: The human NPC cell line CNE-2 was treated with baicalein at low (20 μmol/L), medium (40 μmol/L) and high (80 μmol/L) concentrations. The effects of baicalein on cell proliferation, apoptosis and invasion were detected by methyl thiazolyl tetrazolium (MTT) assay, flow cytometry and transwell assay. The expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Cleaved-caspase 3, FOXO-1, p-FOXO-1 and NF-κB in each group were evaluated by Western blot (WB) analysis. The animal model of NPC was established and treated with baicalein (50 mg/kg), the weight and volume of tumor were measured. Histopathological changes were detected by hematoxylin-eosin (HE) staining. The expressions of FOXO-1, p-FOXO-1 and NF-κB were detected by WB. Results: Compared with the control group, the proliferation and invasive ability of CNE-2 decreased while the rate of cell apoptosis increased with the increase in the concentration of baicalein (p < 0.05). Compared with the control group, as the concentration of baicalein increased, the expression of TNF-α, IL-1β, IL-6, Bcl-2, p-FOXO-1 and NF-κB decreased while the expression of Bax and Cleaved-caspase 3 increased (p < 0.05). There was no significant change in the expression of FOXO-1 in each group. In the animal model of NPC, tumor in the control group grew rapidly and the tumor cells were closely arranged, whereas in the baicalein treated group, the tumor grew slowly and the cells were loosely arranged. There was no significant difference in the expression of FOXO-1 between the control and baicalein group (p > 0.05). However, the expressions of p-FOXO-1 and NF-κB were lower in the baicalein group compared to the control group (p < 0.05). Conclusion: Baicalein exerts anti-tumor effects in NPC by blocking the activation of the FOXO-1/NF-κB pathway, inhibiting the proliferation and invasion of tumor cells, up-regulating the level of cell apoptosis, and down-regulating the expression of inflammatory factors.