Journal Article

Anlotinib as a promising inhibitor on tumor growth of oral squamous cell carcinoma through cell apoptosis and mitotic catastrophe

Liao, Wei, Zhong, Guihua, He, Chao, Liu, Zhigang, Deng, Zhaoming, Wei, Wei, Liu, Qiaodan, Zhang, Hongbo, Xu, Xiwei, Liang, Jun

2021

Overview

Background Oral squamous cell carcinoma (OSCC) has been one of the most malignant cancers in head and neck region. Anlotinib is a tyrosine kinase inhibitor targeting several receptors such as vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR), platelet-derived growth factor receptor (PDGFR) and c-Kit. Here we investigated whether Anlotinib have any antitumor effect on oral cancer and tried to explore and explain the possible mechanism. Methods Data from The Cancer Genome Atlas and the Gene Expression Omnibus and Gene Expression Omnibus database was collected to analyze the relationship between the expression of vascular epithelial growth factor receptor 2 and the overall survival rate of OSCC. Oral cancer cell lines Cal-27 and SCC-25 were cultured to conduct all the experiments. In vitro experiments such as CCK-8, colony formation, cell cycle assay and cell apoptosis assay were conducted to detect cell proliferation ability and the change of cell phase and apoptosis. Proteins concerning cell cycle and cell apoptosis were visualized via western blot. α-Tubulin were visualized via immunofluorescence to detect cells undergoing mitotic catastrophe. Results Higher expression of VEGFR-2 was significantly related to poorer prognosis. Experiment in vitro demonstrated that cell proliferation was significantly inhibited(p < 0.05) after Anlotinib administration and G2/M arrest and apoptosis were both detected in both cell lines. Cycle-related proteins promoting cell cycle progression and proteins related to cell survival were downregulated in Anlotinib group compared to the control group. Cell-death-related biomarker and phosphorylated histone 3 were upregulated in expression in Anlotinib group. Abnormal spindle apparatus was observed in cells undergoing mitotic catastrophe. Conclusions Anlotinib could exert an antitumor effect on oral cancer cell lines via apoptotic pathway and mitotic catastrophe pattern, presenting a promising potential therapy for patients with OSCC.

• Publisher: BioMed Central,Springer Nature B.V,BMC
• Subject: Anlotinib / Antibodies / Antitumor activity / Apoptosis / Biomedical and Life Sciences / Biomedicine / c-Kit protein / Cancer Research / Cell Apoptosis / Cell Biology / Cell cycle / Cell cycle arrest / Cell death / Cell growth / Cell proliferation / Cell survival / Cholecystokinin / Enzyme inhibitors / Fibroblast growth factor 2 / Fibroblast growth factor receptors / Fibroblasts / Gene expression / Genomes / Histones / Immunofluorescence / Kinases / Medical prognosis / Mitotic catastrophe / Oral cancer / Oral squamous cell carcinoma / Platelet-derived growth factor / Primary Research / Protein-tyrosine kinase / Proteins / Squamous cell carcinoma / Tobacco / Tubulin / Tumor cell lines / Vascular endothelial growth factor / Vascular endothelial growth factor receptors / VEGFR-2