Rui-huan Gan,1,* Li-song Lin,2,* Jing Xie,35,* 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, Peoples Republic of China; 2Department of Oral and Maxillofacial Surgery, Affiliated First Hospital of Fujian Medical University, Fuzhou 350005, Peoples Republic of China; 3Department of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350000, Peoples Republic of China; 4Key Laboratory of Stomatology of Fujian Province, School and Hospital of Stomatology, Fujian Medical University, Fuzhou 350004, Peoples Republic of China; 5Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou 350122, Peoples Republic of China

*These authors contributed equally to this work

Correspondence: You-guang LuDepartment of Preventive Dentistry, School and Hospital of Stomatology, Fujian Medical University, 246 Yang Qiao Middle Road, Fuzhou 350000, Peoples Republic of ChinaTel +86 591 8373 6429Fax +86 591 8372 0599Email fjlyg63@fjmu.edu.cn

Xian-e 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, Peoples Republic of ChinaTel +86 138 0951 6580Fax +86 591 8372 0599Email fmuxe@163.com

Purpose: 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

This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License.By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Link:
FLI-06 Intercepts Notch Signaling And Suppresses The Proliferation And | OTT - Dove Medical Press