Study On The Mechanism Of Bufalin Affecting Metabolism Of Lung Adenocarcinoma By Regulating P38γ Signal Pathway

Objective: This study attempts to explore the mechanism of bufalin in inhibiting lung adenocarcinoma based on p38 γ signal pathway.We focus on the effect of bufalin on metabolic reprogramming of lung adenocarcinoma and try to provide new theoretical and experimental basis for bufalin in the treatment of lung adenocarcinoma.Methods: 1.We used Kaplan-Meier survival curve to analyze the correlation between overall survival and p38γ expression in patients with different pathological types of lung cancer.2.We treated human lung adenocarcinoma cell line A549 with bufalin,a traditional Chinese medicine monomer.We observed the expression changes of p38 γ and its related signal pathway proteins by Westernblot experiment.3.We established the animal model of lung adenocarcinoma by subcutaneous inoculation of A549 cells.We divided them into groups and intervened with different concentrations of bufalin and cisplatin.Finally,we evaluated the inhibitory effect of bufalin on lung adenocarcinoma.4.The tumor tissues of lung adenocarcinoma after drug intervention were analyzed by non-targeted metabonomics,and the effects of bufalin and cisplatin on lung adenocarcinoma were analyzed.Results: 1.The expression level of p38γ has no significant correlation with the overall survival rate（OS）of patients with lung squamous cell carcinoma,but has a significant negative correlation with the overall survival rate of patients with lung adenocarcinoma.2.Bufalin inhibited the expression of p38γ and energy metabolism related proteins（p-PFKFB3）in lung adenocarcinoma cell line A549.3.Both bufalin and cisplatin inhibited the growth of subcutaneous transplanted tumor of lung adenocarcinoma in nude mice.4.The tumor metabolites and metabolic pathway of lung adenocarcinoma implanted subcutaneously in nude mice treated with bufalin were changed.Conclusion: The expression level of p38γ is negatively correlated with the overall survival rate of patients with lung adenocarcinoma,suggesting that p38γ may promote lung adenocarcinoma.Bufalin may inhibit the development of lung adenocarcinoma by inhibiting the expression of p38γ and tumor energy metabolism.Bufalin inhibited the growth of subcutaneous implanted tumor of lung adenocarcinoma in nude mice.Bufalin affects the tumor metabolic pathway and signal pathway of lung adenocarcinoma,including adenosine triphosphate binding box transport,arachidonic acid metabolism,platelet activation and so on.