CDK4/6 Inhibitor,abemaciclib Affects The Malignant Biological Behaviors Of Nasopharyngeal Carcinoma Cells

Background: Abemaciclib is a kind of selective CDK4/6 inhibitor that inhibits Rb protein phosphorylation by blocking the formation of Cyclin D1-CDK4/6 complex,thus inducing G1 phase arrest and inhibiting cell growth.It has been shown that abemacicilb is associated with the malignant biological behaviors of a variety of tumors and has been approved by the U.S.FDA for the first-line treatment of breast cancer.There is a study reporting that abemaciclib could inhibit the growth of HNSCCs.But there is few researches about the relationship of abemaciclib and nasopharyngeal carcinoma(NPC),so the main purpose of our study is to investigate the effect of abemaciclib on the growth,EMT and radiosensitivity of human NPC cell lines.Methods: In this study,we use CCK8 assays to detect the effect of abemaciclib on growth of NPC cell lines HNE1 and CNE2 firstly.Secondly,western blot was conducted to detect the expression level of EMT-related proteins.Meanwhile,the scratch experiment was conducted to study the effect of abemaciclib on the migration ability of NPC cell lines.Then,the effect of abemaciclib on the sensitivity of nasopharyngeal carcinoma cell lines to radiotherapy was evaluated by clonal formation experiment after irradiation of NPC cell lines.And the mechanism of action was further explored by flow cytometry and western blot.Results: We first found that CDK4/6 inhibitor abemaciclib could inhibit the growth of human nasopharyngeal carcinoma cell lines HNE1 and CNE2 by CCK8 assay.Then,it was revealed that abemaciclib could regulate the expression of EMT-related proteins and inhibit the migration of nasopharyngeal carcinoma cells.What’s more,after the addition of abemaciclib,the apoptosis and G2/M stage arrest of nasopharyngeal carcinoma cells increased,and the phosphorylation of Rb repressed,resulting in increased radiosensitivity.Conclusions: Abemaciclib can inhibit the malignant biological behavior of human NPC cell lines and can be used as a potential target for the treatment of human NPC.