Propofol Regulates the Proliferation and Migration of Lung Cancer Cells Through Atr Signaling Pathway
Abstract Aims: Here we aim to investigate the regulation of propofol on DNA damage caused by replication fork arrest in esophageal squamous cell carcinoma cells.Methods: A549 and NCI-H460 cells were treated with propofol and hydroxyurea (HU) in vitro. CCK-8 assay was used to examine cell proliferation. Transwell assay was employed to investigate cell migration and invasion abilities. Western blotting was carried out to study the activities of ATR signals. Laser confocal microscopy was utilized to study the formation of p-RPA32 foci.Results: Propofol treatment promoted the apoptosis and suppresses the proliferation, migration and invasion, possibly by increasing the sensitivity of A549 and NCI-H460 cells against DNA damage. Propofol treatment enhanced the sensitivity of A549 and NCI-H460 cells to damages caused by replication fork arrest, as well as the activity of ATR signaling pathway. Propofol regulated the sensitivity of A549 and NCI-H460 cells to DNA replication damage by affecting the level of H3K27me3.Conclusions: The present study demonstrates that propofol up-regulates the expression of H3K27me3 in lung cancer cells, promotes the recruitment of exonuclease MUS81 in stagnant replication fork, induces apoptosis caused by DNA damage, and thus inhibits the proliferation and metastasis of tumor cells.