Effects Of Docosahexaenoic Acid On Gene Expression Profiles Of Colorectal Transplanted Tumors In Mude Mice

Background The inhibiting effects of docosahexaenoic acid (DHA) on thetumorigenesis of prostatic cancer, mammary cancer, and colorectal cancer have been foundby epidemiology investigations. Both in vivo experiments and in vitro tests suggested thatpathogenesis of colon cancer and proliferation of colon cancer cell could be inbibited byDHA treatment, but the underlying mechanism(s) were not elucidated yet.Objective The aim of this study is to explore the molecular mechanisms of DHAinhibiting the occurrence and development of colon cancer, using the new moleculartechniques.Methods To establish animal model of colorectal transplanted tumors, HCT-15coloncancer cells were subcutaneously implanted in mude mice. After fed with feeding stuffwith or without DHA for eight weeks, the effects on growth of colorectal transplantedtumors was evaluated. Effects of DHA on gene expression profiles of colorectaltransplanted tumors in mude mice were evaluated by mRNA microarray. Differentiallyexpressed genes were determined to analyze genes functions and involved signal pathways.Then semi-quantitive reverse transcriptase polymerase chain reaction (RT-PCR) wasperformed in mude mice xenografts and HCT-15cells for validation of selected genesexpression based on microarray results.Results1) The volumes of colorectal transplanted tumors in the DHA group weresignificantly decreased, compared with the control group.2) A total of2073differentiallyexpressed genes were detected by gene chip screening.1106genes were down-regulatedafter DHA treatment. The dysregulated genes include matrix Gla protein, immunoglobulinkappa associated proteins and transcription initiation factor TFIID subunit11associatedproteins.3) Bioinformatic analysis showed that the up-regulated genes were associatedwith binding, protein binding, substrate-specific transport and cytoskeleton. Thedown-regulated genes were classified into several types, including transporter activity,receptor binding, transmembrane transporter activity, substrate-specific transporter activity, structural molecule acticity, substrate-specific transmenbrane transporter activity, iontransmenmbrane transporter activity, identical protein binding, protein dimerzation activity,calcium ion binding, and sequence-specific DNA binding. Both in vivo and in vitro,expressions of cyclooxygenase2(COX2), hypoxia-inducible factor-1α (HIF-1α), vascularendothelial growth factor-A (VEGF-A), cartilage oligomeric matrix protein (COMP),matrix metalloproteinases-1(MMP-1), matrix metalloproteinases-9(MMP-9), sterol sarlierprotein2(SCP2), and syndecan3(SDC3) were significantly decreased by DHA feeding,which is consistent with the results of mRNA array.Conclusions DHA exerts an anti-cancer effect on xenografts of colon cancer in nudemice, which is associated with mutiple functional pathways including angiogenesis andmatrix metalloproteinases.