Enhancement Of Radiosensitivity For Esophageal Squamous Cell Carcinoma By CDK4/6 Inhibitor

Objective : To explore the effect of CDK4 / 6 inhibitor on the radiosensitivity of esophageal squamous cell carcinoma and its possible molecular mechanism.Methods:To determine the effects of CDK4 / 6 inhibitor on the sensitivity of radiotherapy to esophageal squamous cell carcinoma cells through cell culture,cell irradiation,CCK8,and cell clone formation experiments;To explore the molecular mechanism of CDK4 / 6 inhibitor on the radiosensitivity of esophageal squamous cell carcinoma cells,western Blot,cellular immunofluorescence and small molecular inhibitor was used.Results:CCK8 and cell clone formation experiments showed that CDK4 / 6 inhibitors can synergistically inhibit cell proliferation and colony formation.Cell immunofluorescence experiments showed that the CDK4 / 6 inhibitor combined with the radiation significantly increased the level of γH2AX compared with the radiation alone group.Western Blot experiments suggest that combining CDK4 / 6 and radiation reduces the expression levels of RAD51 and Cyclin D1 compared to radiation alone,suggesting that CDK4 / 6 exerts a sensitizing effect by inhibiting radiation-induced DNA damage repair.In addition,in our experiments,Western Blot analysis found that combined with CDK4 / 6 and radiation,the main form of cell death is autophagy,and the use of autophagy inhibitor could reverse the radiosensitization effect of CDK4/6 inhibitor.Conclusion: CDK4 / 6 inhibitor combined with radiation increases the radiosensitivity of esophageal squamous cell carcinoma cells.The possible mechanisms of this effect are the inhibition of the radiation-induced DNA damage repair pathway and the induction of autophagic cell death.