The Mechainism Of Anti-tumor Of Usnic Acid In Human Gastric Cancer In Vitro And In Vivo

BackgroundUsnic acid(UA)has been demonstrated as a secondary metabolite of certain lichen species,which shows the properties of anti-tumor,anti-oxidant and anti-inflammatory in a wide variety of tumor cells,yet its role in cancer of the stomach is not very clear.ObjectiveThe investigation focus on two aspects:the anticancer effect of usnic acid in vitro and in vivo in gastric carcinoma cells;potential molecular mechanisms.Material/MethodsBGC823 and SGC7901 human gastric cancer cell lines were object of study.Vitro experiments:CCK8 assay was employed to measure cell proliferation;Flow Cytometry was applied to analyze the arrest of cell cycle;Hoechst33258 staining assay was used to examine cellular apoptosis;Western blot assay was exerted to determine cycle-associated proteins(CyclinDl,P21,CDK1,CyclinB),apoptosis-related proteins(cleaved-caspase3,cleaved-PARP,Bax,Bcl2)and autophagy-associated proteins(LC3-?and P62)expression.Vivo experiments:BGC823 tumor-bearing mouse model was established;H&E staining and immunohistochemistry were used to measure the protein expression(Bax and Bcl2)of tumor tissues.ResultsIn vitro experiments,usnic acid can significantly suppress the cell proliferation in BGC823 and SGC7901 gastric cancer cells in dose dependent and time dependent manner.And it can induce G1 phase arrest(gastric cancer BGC823)and G2 phase arrest(gastric cancer SGC7901)with no dose dependent manner.Moreover,it can promote cells apoptosis in BGC823 and SGC7901 gastric cancer cells.Apart from that,the protein expression levels of P21,Bax,cleaved-caspase3,cleaved-PARP,and LC3-II were elevated while the expression levels of CyclinD1,CDK1,CyclinB,Bcl2 and P62 were decreased.In vivo experiments,UA treatment was significantly more eff ective in inhibiting the tumor growth and in modulating the level of Bax and Bcl2 in tumor tissues than 5-FU treatment without reducing the body weight.ConclusionsUsnic acid can induce autophagy,induce cycle arrest by adjusting the cycle related proteins and can induce apoptosis by activating caspase cascade and regulating the expression of Bcl2 family proteins in BGC823 and SGC7901 gastric cancer cells.Moreover,compared to 5-FU,it shows more anti-tumor effect by regulating the Bcl2 family proteins in BGC823 tumor-bearing models.