Effects Of Palmitic Acid-rich Diet On Tumor Growth And Epithelial-mesenchymal Transition In Prostate Cancer Mice

High-fat diet is an important risk factor for the development of prostate cancer.Palmitic acid is the most common saturated fatty acid in the diet and the main product of FASN.Many studies have shown that FASN is highly expressed in many cancers,and the increase of FASN expression level will lead to the increase of synthetic fatty acids in vivo.It has been reported that the proliferation of tumor cells depends on endogenous fatty acid synthesis.However,the effect of palmitic acid-rich diet on the occurrence and development of prostate cancer is rarely reported.Therefore,this research aims to study the effects of palmitic acid-rich diet on tumor growth and epithelial-mesenchymal transition(EMT)in prostate cancer DU145 cells,prostate cancer transplanted mice and primary prostate cancer mice with over-expression of c-Myc gene(hereinafter expressed as c-Myc~T).These studies will provide new ideas for the remission of prostate cancer.The main research results of this paper are as follows:(1)The difference of FASN expression between prostate cancer and non-cancerous prostate tissues.was investigated by searching the TCGA(The Cancer Genome Atlas)database and performing immunohistochemical(IHC)staining.The results showed that FASN expression in prostate cancer tissue was significantly higher than that in non-cancerous prostate tissue(P<0.001).FASN expression was significantly higher in prostate cancer tissue with high Gleason score.(2)The effects of exogenous palmitic acid on proliferation and migration of prostate cancer cell-DU145 were investigated in vitro.MTT assay was used to detect cell proliferation,and the results showed that DU145 cells treated with 10?M palmitic acid for 72 h could significantly enhance cell proliferation(P<0.05).Clone formation experiment showed that DU145 cells treated with 10?M palmitic acid for 15 days formed more colonies than the control group(P<0.05).The results of wound healing assay showed that DU145 cells treated with 10?M palmitic acid for 48 h can significantly improve the migration ability of cells(P<0.01).(3)The effects of high palmitic acid-rich diet on the growth of prostate tumor and EMT process were studied by using nude mice transplanted with prostate cancer and c-Myc~Tmice.By analyzing the growth of prostate tumor,the results show that palmitic acid-rich diet can promote the growth of transplanted prostate cancer and promote the growth of prostate tumor in c-Myc~Tmice.The expression of EMT-related markers such as TGF-?1,E-cadherin and N-cadherin in tumor was detected by IHC staining and western blot.The results showed that palmitic acid-rich diet could induce EMT process and activate TGF-?1 signal in nude mice transplanted with prostate cancer and c-Myc~Tmice.(4)To explore the relationship between CD36 and TGF-?1 in prostate cancer clinical specimens by searching TCGA database.The relationship between TGF-?1 and the survival rate of prostate cancer patients was analyzed by Kaplan-Meier survival method.The results showed that the expression of TGF-?1 was related to the decrease of survival rate of prostate cancer patients(P=0.001).Gene correlation analysis showed that the expression of CD 36was positively correlated with the expression of TGF-?1(P<0.001).Univariate and multivariate COX regression analysis showed that TGF-?1,TGF-?RI and CD36 were risk factors of prostate cancer(HR>1),and TGF-?1 was an independent risk factor of prostate cancer(P<0.05).To sum up,this paper verifies that FASN is highly expressed in prostate cancer and proposes that FASN expression is positively correlated with the incidence of prostate cancer.Palmitic acid-rich diet can promote the prostate cancer xenografts and the development of prostate cancer in c-Myc~Tmice,and induce epithelial-mesenchymal transition,which may be related to its up-regulation of TGF-?1 expression.It can provide some reference for future dietary guidelines,that is,moderate amount of palmitic acid should be taken in daily diet.