<p>Icariin Mitigates the Growth and Invasion Ability of Human Oral Squamous Cell Carcinoma via Inhibiting Toll-Like Receptor 4 and Phosphorylation of NF-κB P65</p>

Abstract

Background: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy worldwide. Icariin (ICA), an active ingredient of flavonoids, has been demonstrated to possess antitumor activity in diverse cancers. Whereas, the role of ICAin OSCC is still unclear. Methods: Herein, we investigated the anti-tumor effects of ICA in vitro and in vivo. CCK-8, colony formation and trans-well assay were used to examined viability, proliferation and invasion in SCC-9 and SCC-15 cell lines, respectively. Next, we tested the expression of tolllike receptor 4 (TLR4) and NF-κB P65 by western blot or immunofluorescence staining. Finally, we constructed a xenograft mice model to investigate the effect of ICA in vivo. Results: In vitro, ICA decreased the human oral squamous cells viability, proliferation and invasion in a concentration-dependent manner. Besides, ICA decreased the phosphorylation level of P65 and down-regulated TLR4 protein. In vivo, compared with control, ICA significantly suppressed the tumor size and weight. In addition, ICA downregulated the levels of Ki67 and VEGF markedly. Dramatically, ICA decreased the phosphorylation level of P65 in tumor tissues. Conclusion: Taken together, ICA could act as a anticancer drug against OSCC to mitigate the growth and invasion ability, the underlying mechanism may due to the down-regulation of TLR4/NF-κB signaling.

Icariin, an Up-and-Coming Bioactive Compound Against Neurological Diseases: Network Pharmacology-Based Study and Literature Review

“… 191 Icariin exhibited antiangiogenic effects in xenograft models of tumors including hepatocellular carcinoma and renal cell carcinoma, 192 and suppressed tumor cell migration and invasion by regulating the Rac1-dependent vasodilator-stimulated phosphoprotein (VASP) pathway. 193 Icariin also enhanced the effects of antineoplastic drugs and radiation therapy; in one study, the combination of icariin and gemcitabine resulted in an enhanced antitumor effect compared to either drug alone, 194 highlighting its therapeutic potential for cancer treatment.…”

Influence of icariin on inflammation, apoptosis, invasion, and tumor immunity in cervical cancer by reducing the TLR4/MyD88/NF-κB and Wnt/β-catenin pathways

“…Recently, Hao et al observed that ICA can significantly induce antitumor immunity in murine B16F10 melanoma and MC38 colorectal tumors mice in a CD8 T-cell-dependent way [ 19 ]. In addition, ICA has been demonstrated to attenuate the growth and invasion ability of Human oral squamous cell carcinoma in vitro and in vivo by inducing the down-regulation of Toll-Like Receptor 4 (TLR4)/ NF-κB pathway [ 20 ]. Also, Huang et al demonstrated that ICA inhibited the growth of HeLa cervical cancer cells dose-dependently via inhibiting the mTOR/PI3K/AKT signaling cascade [ 21 ].…”

Toll‐like receptors in health and disease

“…In OSCC, in addition to increased TLR4 expression, the distribution of TLR4 likewise increased from the basal hominins to the spiny layer. 215 , 216 In addition, several researchers have suggested that TLR4 overexpression promotes OSCC development and proliferation and is closely associated with poor invasion and metastasis in oral cancer patients. 217 , 218 , 219 , 220 , 221 , 222 These findings demonstrated a strong correlation between TLR4 and the onset and progression of OSCC.…”