The Effect And Mechanism Of Dexmedetomidine On Lung Cancer

Objective: The use of anesthetics during surgery can affect tumor progression.Dexmedetomidine(Dex)is one of the commonly used anesthesia drugs in clinic and the effect of Dex on lung cancer is not clear.In this paper,we explored the the effects of dexmedetomidine on lung cancer cells(A549 and H1299)proliferation,apoptosis,migration,epithelial-mesenchymal transition(EMT),stemness,drug resistance,and Wnt/ ?-catenin signaling pathway,and studied the relevant mechanisms involved,which would provide guidance for the selection of anesthetics for patients with lung cancer.Methods: After treatment with Dex,(1)Cell counting Kit-8(CCK8)and clone-formation assays were used to detect cell proliferation;(2)Flow cytometry was adopted to analyze cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins(Bax and Bcl-2);(3)Transwell migration assay was performed to detect cell migration,and western blot and immunofluorescence were used to detect the expression of N-cadherin,vimentin and E-cadherin;(4)q RT-PCR,western blot and immunofluorescence were performed to detect the m RNA or protein expression of stemness-related factors(Sox2,Oct4,Nanog)of the lung cancer cells;(5)CCK8 assay was used to evaluate the effect of Dex on Cis-induced cytotoxicity against lung cancer cells,and immunofluorescence was used to detect the effect of Dex and Cis on the expression of Sox2 and Oct4;(6)Western blot and immunofluorescence were adopted to detect the effect of Dex on the expression of Wnt/?-catenin signal pathway related proteins(?-catenin,CD44,Cyclin D3).Results :(1)Dex inhibited the activity and colony formation of lung cancer cells(A549 and H1299);(2)Dex induced apoptosis and Bax expression of lung cancer cells,and reduced the expression of Bcl-2;(3)Dex reduced the migration ability and the expression of N-cadherin and Vimentin of lung cancer cells,and promoted E-cadherin expression;(4)Dex inhibited the expression of Sox2 and OCT4 of lung cancer cells;(5)Dex could enhance the inhibitory effect of Cis on the activity of lung cancer cells and the expression of Sox2 and Oct4;(6)Dex could reduced the expression of ?-catenin,CD44 and Cyclin D3 in lung cancer cells.Conclusions: Dex could inhibit the proliferation of lung cancer cells,induce apoptosis,inhibit cell migration and EMT progress,reduce cell stemness,enhance the cytotoxicity of Cis,and inhibit Wnt/?-catenin signaling pathway.This study elucidated the effect of Dex on lung cancer cells,thus providing a guidance for perioperative anesthesia of lung cancer patients.