The Effect Of Peroxisome Proliferator-activated Receptor β/δ On HepG2 Transplanted Tumor In Nude Mice

Objeetive:The peroxisome proliferator-activated receptor β/δ(PPARβ/δ)is a gene regulatory transcription factor involved in various metabolic processes in the human body.When it is activated by ligand binding,it can be combined with the promoter response element of the target gene to participate in the regulation of gene transcription.At present,many literatures have shown that PPARβ/δ can accelerate fatty acid metabolism,increase insulin sensitivity,inhibit inflammation and increase muscle fiber oxidation to improve athletic performance.However,there is controversy regarding the role of PPARβ/δ in promoting or suppressing cancer,especially in primary liver cancer.Previous studies of the research group suggested that PPARβ/δ inhibited hepatocellular carcinoma.However,these are the results of in vitro experiments.It is not clear whether the effect of the PPARβ/δ in the in vivo environment will play a role in the receptor environment and its components.Human hepatocellular carcinoma cell transfected with PPARβ/δ gene and wild-type human hepatoma cell xenograft model in nude mice by detecting tumor-associated proteins in two human hepatocellular carcinoma xenograft models to investigate peroxisome proliferator-activated receptor β/δ The specific role of human hepatocarcinogenesis and its possible mechanisms.Methods:Wild type Hep G2 human hepatocellular carcinoma cell line and PPARβ/δ gene transfected Hep G2 human hepatoma cell line were inoculated on the outside of right upper limb of BALB/c(nu/nu)mice to construct human hepatocellular carcinoma xenograft tumor nude mice model,namely control group and experiment.Both groups were fed with normal feed.After about 4 weeks,all experimental mice were sacrificed by cervical dislocation.The transplanted tumor tissue was dissected and tissue specimens were taken.Immunohistochemical SP method was used to detect the expression of p-Akt,p-m TOR,caspase 3,vimentin,E-cadherin,and Ki-67 in the two groups of tumor tissues.Resuits:Both the groups of PPARβ/δ gene transfected into human hepatocellular carcinoma cells and wid-type human hepatocellular carcinoma cells were all capable of tumor formation.The tumor growth of all groups of nude mice was slow.On the28 th day after administration,the transplanted tumor volume of the wild-type human hepatoma-bearing tumor was smaller than that of the experimental group,but there was no statistically significant difference among the other groups at all other time points.The expression of p-Akt,m TOR,Vimentin,and Ki-67 in the experimental group was significantly lower than that in the normal control group.The difference was statistically significant(P<0.05),while the E-cadherin expression was significantly higher than that of the normal control group.There was statistically significant differences(P<0.05);caspase 3 was expressed in both the experimental group and the normal control group,with no significant difference(P>0.05).Conclusion:In a nude mouse model of human hepatocellular carcinoma xenografts,the expression of PPARβ/δ has apotential inhibitory effect on Hep G2 human hepatocellular carcinoma metastases.It may inhibit cell apoptosis induced by activation of PI3K/Akt/m TOR pathway,inhibit cell survival,and at the same time,inhibit and epithelial-to-mesenchymal transition(EMT)inhibit the migration and proliferation of hepatoma cells,thereby inhibiting the occurrence and development of tumors.