Icariin inhibits oral squamous cell carcinoma cell proliferation and induces apoptosis via inhibiting the NF-κB and PI3K/AKT pathways.

Abstract

Oral squamous cell carcinoma (OSCC), one of the most common types of human cancer, has a high mortality rate and a poor prognosis due to its high rates of recurrence and metastasis. In recent years, icariin (ICA) has been reported to play an important role in a variety of malignancies, such as gastric, colorectal, pancreatic and ovarian cancer. However, its role and mechanism in OSCC remains to be elucidated. The present study aimed to investigate the effect of ICA in OSCC cells and to reveal its underlying mechanisms. The OSCC cell lines SCC9 and Cal 27 were used to explore the effect of different concentrations of ICA on the biological behavior of OSCC cells. The effect of ICA on OSCC cell proliferation and apoptosis was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide and flow cytometric assays, respectively. Subsequently, the protein expression levels of caspase-3 and cleaved-caspase-3 were detected using western blot analysis. Additionally, the protein and mRNA expression levels of nuclear factor-κB (NF-κB) and phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) signaling pathway-related factors were determined using western blot analysis and reverse transcription-quantitative PCR, respectively. The results demonstrated that ICA inhibited OSCC cell proliferation and significantly increased the apoptosis rate in a dose-dependent manner. In addition, treatment of OSCC cells with ICA upregulated the protein expression of cleaved-caspase-3 and increased the cleaved-caspase-3/caspase-3 ratio. The protein expression levels of phosphorylated (p)-p65, p-PI3K and p-AKT were decreased in OSCC cells treated with ICA. The aforementioned findings revealed that ICA could attenuate the proliferation of OSCC cells and induce apoptosis via inhibiting the NF-κB and PI3K/AKT signaling pathways. Therefore, the current study provided a new insight into the clinical treatment of OSCC.