Deguelin And 7-hydroxy-substituted Deguelin Derivative Antitumor Actives In Vitro And In Vivo

Objevtive:Deguelin is a derivative of rotenone derived from Mundulea sericea.Deguelin has broad spectrum of anti-tumor activity by regulating different pathways,such as lung cancer,breast cancer,colon cancer,lymphoma and so on.However,deguelin can cause damage to the heart,lung and nervous system,which is the main reason why deguelin can not be used as an anti-tumor drug.In order to improve the side effects of deguelin,we synthesized 7-hydroxy-substituted deguelin derivative containing dissociative hydroxyl based on the structure of deguelin,then explored the antitumor activities of deguelin and 7-hydroxy-substituted deguelin derivative.Methods:1.Synthesis deguelin and 7-hydroxy-substituted deguelin derivative,then explore their anti-proliferative and induced apoptotic activities to H1299 lung cancer cells and MCF-7 breast cancer cells in vitro.2.At the molecular level,using fluorescent quantitative PCR and Western Blotting to detect the expression of apoptosis factors in H1299 cells and MCF-7 cells before and after treatment of deguelin and 7-hydroxy-substituted deguelin derivative.3.In vivo experiment:Establish H1299 lung cancer transplantation model,deguelin and 7-hydroxy-substituted deguelin derivative for drug intervention experiments to explore the anti-tumor activity of the drug in vivo.Results:1.According to the results of CCK-8,the proliferation of H1299 cells and MCF-7 cells can be inhibited by deguelin and 7-hydroxy-substituted deguelin derivative,and showed time-dose dependence.AO-EB method was used to stain H1299 cells and MCF-7 cells before and after the drug treatment,from the results of staining and cell morphology,the activity of apoptosis was induced by deguelin and 7-hydroxy-substituted deguelin derivative.Annexin V-FITC/PI flow cytometry was used to quantify the apoptosis of H1299 cells and MCF-7 cells induced by the two drugs,and the drug concentration was proportional to the apoptosis rate of tumor cells.2.qPCR and Western Blotting experiments showed that the expression levels of ATM?Bax?PUMA?and Caspases-3 in H1299 cells and MCF-7 cells could be up-regulated by deguelin and 7-hydroxy-substituted deguelin derivative,thereby inducing apoptosis.3.Deguelin and 7-hydroxy-substituted deguelin derivative can inhibite the growth of H1299 cell nude mouse xenograft,and the living status of nude mice was not affected significantly.