FLI-06 Intercepts Notch Signaling And Suppresses The Proliferation And Self-renewal Of Tongue Cancer Cells

Abstract

Rui-huan Gan,1,* Li-song Lin,2,* Jing Xie,3–5,* Li Huang,2,4 Lin-can Ding,2 Bo-hua Su,2 Xian-e Peng,1,5 Da-li Zheng,4,5 You-guang Lu1,3 1Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou 350122, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, Fuzhou 350005, People’s Republic of China; 3Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350000, People’s Republic of China; 4Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, People’s Republic of China; 5Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350122, People’s Republic of China*These authors contributed equally to this workCorrespondence: You-guang LuDepartment of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou 350000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected] PengDepartment of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, 1 Xue Yuan Road, University Town, Fuzhou 350122, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: The Notch signaling pathway plays an oncogenic role in tongue squamous cell carcinoma. The aim of this study was to inhibit the proliferation and self-renewal of tongue cancer cells by applying Notch signaling pathway inhibitor FLI-06 (Selleck, USA) and to lay a foundation for the clinically targeted treatment of tongue cancer for the future.Methods: The mRNA expression level of Notch1 and the overall survival rate of patients with tongue cancer were examined by analyzing the TCGA database. Tongue cancer cells were treated with FLI-06. Cell proliferation, apoptosis, and stem cell self-renewal ability were tested in appropriate ways. A xenograft mouse model was established to observe tumor growth.Results: From the TCGA data, we demonstrated that patients with high expression of Notch1 had a poor prognosis. We observed that the Notch signaling pathway inhibitor FLI-06 can restrain the activation of the Notch signaling pathway, decrease cell proliferation and induce cell apoptosis in vitro. The xenograft experiment indicated that intraperitoneal injection of FLI-06 inhibited tumor growth and increased cell apoptosis. FLI-06 suppressed both the mRNA and protein expression of Notch receptor and Notch targeted genes. We also observed that FLI-06 suppressed the proliferation of tongue cancer stem cells.Conclusion: FLI-06 can block the proliferation and self-renewal of tongue cancer cells. It is inferred that this compound, which inhibits the Notch signaling pathway, may serve as a potential targeted drug for the treatment of tongue cancer in the clinic.Keywords: tongue cancer, Notch signaling pathway, Notch inhibitor, cancer stem cells

Keywords

• Tongue cancer
• Notch signaling pathway
• Notch inhibitor
• Cancer stem cells