Study Of The Different Effects And Mechanisms Between EPA And DHA On Prostate Cancer Based On Transcriptome Analyses

Prostate cancer is the most common malignancy in men.According to the epidemiological studies,Omega-3 polyunsaturated fatty acids could regulate numerous signaling pathways in intracellular and extracellular to inhibiting the growth,apoptosis and metastasis of cancer cells,especially eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA).The study found that there are some distinct biological functions and mechanisms in reducing cardiovascular disease and inhibiting inflammation.However,there are still many controversies in the effect of EPA and DHA on cancer,especially in prostate cancer.Therefore,we used the xenograft model to explore the different influence by supplementation EPA or DHA on prostate cancer.And then,based on transcriptome analyses,we studied the different expression genes and do some function enrichment to explain the distinction between EPA and DHA form the level of gene.The main results of this paper are as follows:(1)Dietary supplementation of EPA could significantly inhibit the growth of prostate tumors,and the effects was better than that of DHA.For example,by measuring the weight and volume trend of human prostate LNCaP cell transplantation tumor,it was found that the weight of mice supplemented with EPA was 36.60% less than that of dietary supplement DHA,and the tumor growth curve was more slower;The concentration of human prostate specific antigen(PSA)in the serum of mice was measured by enzyme linked immunosorbent assay(ELISA),and it was found that the dietary supplementation of EPA or DHA in the serum of mice supplemented with Omega-6 polyunsaturated fatty acids decreased.The effects of dietary supplementation of EPA or DHA on arachidonic acid in mice were measured by GC-MS,and both EPA and DHA could significantly reduce the content of AA.Therefore,the results showed that although dietary supplementation of EPA and DHA had similar biological functions in inhibiting PSA secretion and arachidonic acid.The contents of total cholesterol(TC)and triglyceride(TG)in serum of mice were determined by biochemical analyzer.It was found that EPA and DHA significantly decreased the content of TC and TG.(2)Based on transcriptome data analysis,it was found that there were differences in gene expression between EPA and DHA compared with negative control group.EPA caused the change of 367 genes,while DHA only caused 192 genes.But The most interesting thing is that just only 24 genes were in common.(3)Through functional enrichment analysis of the selected different expressed genes,247 genes were found to be down regulated by EPA,and 603 GO terms were enriched.There were significant differences in the 33 signaling pathways.We found that EPA could induce multiple signaling pathways including Ras/Rap1 and EPA could inhibit the activity of PI3 K by reducing the expression of PI3KCG/KIT genes directly or by activating RTKs activities which could attract PI3K/AKT/mTOR signaling pathway.(4)Dietary supplement EPA up-regulated the expression of 120 genes.Through functional enrichment analysis of these genes,it was found that these genes affect the membrane structure of the phospholipid bimolecular layer,such as exudate and vesicle,influence the function of lipid rafts,and deduce that it may promote the release of exocrine through lipid rafts and stimulate autophagy of prostate cancer cells.But it has not been found in DHA.Therefore,dietary supplementation of EPA has a better effect on prostate cancer patients.Above all,EPA could efficiently inhibit the growth of human prostate tumor by xenograft model and explore the mechanism based on the transcriptomic,which provide a theory evidence for prostate cancer to supplement EPA.