mln-8237 and Tongue-Neoplasms

Aurora-A kinases are overexpressed in many cancer tissues and cells. Alisertib is an investigational, orally administered, selective, small-molecule Aurora-A kinase inhibitor with preclinical activity against a broad range of tumors. Our study was aimed to detect the effects of alisertib on human tongue squamous cell carcinoma (HTSCC). Treatment of a human tongue squamous cell carcinoma cell line, HSC-3, with alisertib to inhibition of Aurora-A kinases reduced proliferation and induced apoptosis, which was accompanied by activation of the ATM/Chk2/p53 pathway. In vivo, inhibition of Aurora-A kinases in established xenografted tumors decreased tumor size and weight. Kaplan-Meyer survival analysis demonstrated that the cumulative survival time of mice without Aurora-A kinases was significantly longer than those with Aurora-A kinases. Our data provide the basis for developing alisertib to treat human tongue squamous cell carcinoma.

Topics: Animals; Apoptosis; Ataxia Telangiectasia Mutated Proteins; Aurora Kinase A; Azepines; Carcinoma, Squamous Cell; Cell Line, Tumor; Checkpoint Kinase 2; Humans; Mice; Mice, Nude; Protein Kinase Inhibitors; Pyrimidines; Signal Transduction; Tongue Neoplasms; Tumor Suppressor Protein p53; Xenograft Model Antitumor Assays