Mechanism Of Common Fatty Acids Influencing Colorectal Cancer Through PPAR Pathway

BackgroundMalignant tumors are one of the most difficult difficulties faced by human beings in public health in the 21st century,and the current situation of cancer treatment in China is particularly grim.Among them,the incidence of colorectal cancer ranks second in China,and the early onset is hidden,and the degree of malignancy is high,which brings great harm and loss to patients and families.The pathogenesis of colorectal cancer has always been closely related to genetic and environmental dietary factors,especially fatty acids,but its mechanism has not been elucidated.Fatty acid(FA)is an indispensable substance in human body,which plays an important role in energy supply,metabolism,signaling pathway transduction and other life activities.Palmitic acid(PA)is the most common saturated fatty acid in the human body,and studies have shown that it may be involved in the production of a variety of tumors.Conjugated linoleic acid(CLA)is a kind of linoleic acid with conjugated double bond,which has been proved by many studies to have a variety of physiological functions which are quite beneficial to human body.Studies have shown that it may have a certain inhibitory effect on colorectal cancer,but the specific mechanism has not been clarified.Peroxisome proliferator-activated receptor a(PPARα)is a nuclear receptor,whose main function is to regulate energy supply,lipid homeostasis and inflammation,and may be involved in the regulation of colorectal cancer.The WNT pathway is a classic pathway in colorectal cancer,which determines cancer cell proliferation,cell survival and differentiation.Whether CLA and PA regulate colon cancer through PPARa has not been reported.ObjectiveTo explore the molecular mechanism of CLA and PA regulating colorectal cancer cells.MethodsIn this study,RKO and Caco2 of human colon cancer cells were taken as research objects.The conjugated linoleic acid isomer cis-9,trans-11CLA and palmitic acid were used to treat cell lines.The effects of PA and CLA on the proliferation and invasion of colon cancer cells were verified by CCK8 and cell cloning experiments.The effect of PA and CLA on apoptosis of colon cancer cells was verified by flow cytometry,and the effect of PA and CLA on migration of colon cancer cells was verified by scratch assay.Western Blot was used to detect the expression of PPARa,β-catenin and other related proteins in colon cancer cells treated with PA and CLA,and immunofluorescence was used to detect the localization of β-catenin.mRNA expressions of TRIM 11 and TRIM33 after CLA were detected by qPCR.Double luciferase method was used to verify the excitability of PA and CLA on PPARa.Result(1)CLA can inhibit the proliferation of colorectal cancer cells and significantly promote apoptosis,while PA can promote the proliferation of colorectal cancer cells and significantly inhibit apoptosis.CLA inhibits colorectal cancer cell migration and PA promotes it.(2)CLA can down-regulate the expression of β-catenin,while PA can up-regulate the expression of β-catenin.(3)CLA up-regulates PPARa activity from protein level and mRNA level,while PA down-regulates PPARa activity from protein level and mRNA level.However,PPARa interacts with P53,which can regulate the wnt pathway,and CLA and PA may regulate the expression of β-catenin through this pathway.(4)CLA up-regulates the transcriptional activity of TRIM3 3 and down-regulates the transcriptional activity of TRIM 11,thus affecting the ubiquitination degradation of β-catenin.Conclusion1.CLA inhibits proliferation,invasion and migration of colorectal cancer cells and promotes apoptosis in vitro.PA promotes the proliferation,invasion and migration of colorectal cancer cells and inhibits cell apoptosis in vitro.2.Molecular mechanism of CLA and PA regulating the growth and metastasis of colorectal cancer cells:(1)By binding with PPARa,CLA up-regulates the expression of P53,thus inhibiting the expression of β-catenin.On the contrary,PA promoted the expression of β-catenin.(2)CLA affected the ubiquitination degradation of β-catenin by up-regulating the transcriptional activity of TRIM33 and down-regulating the transcriptional activity of TRIM11.