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

Abstract

Ke Lei, 1 Bing Ma, 2 Ping Shi, 2 Che Jin, 3 Tan Ling, 1 Longjiang Li, 4 Xiangyi He, 5 Lunchang Wang 1 1Department of Stomatology, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 2Department of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of China; 3Endodontics Department, Dental Hospital of Lanzhou, Lanzhou 730000, People’s Republic of China; 4State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, People’s Republic of China; 5Department of Prosthodontics, School of Stomatology, Lanzhou University, Lanzhou 730000, People’s Republic of ChinaCorrespondence: Ping ShiDepartment of Respiratory, Central Hospital of Guangyuan, Guangyuan 628000, People’s Republic of ChinaTel/Fax [phone]Email [email protected]: 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 toll-like 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.Keywords: icariin, toll-like receptor 4, oral squamous cell carcinomas, NF-κB

Keywords

• icariin
• toll-like receptor 4
• oral squamous cell carcinomas
• nf-κb