This dissertation, "Effect of Dietary Fatty Acids on Metastatic Hepatocellular Carcinoma" by Yee-ki, Carol, Lee, 李綺琪, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled EFFECT OF DIETARY FATTY ACIDS ON METASTATIC HEPATOCELLULAR CARCINOMA submitted by Yee Ki, Carol, LEE for the degree of Master of Philosophy at The University of Hong Kong in December 2007 The relationships between dietary fatty acids and certain human cancers such as the breast, prostate and colon are well studied but little is known about their effects on liver cancers. This thesis aims to investigate the influence of dietary fatty acids on human hepatocellular carcinoma (HCC). In part one, the anti-proliferation effect of docosahexaenoic acid (DHA), an omega-3 polyunsatuarated fatty acid (ω-3 PUFA) enriched in marine fish oil, on two human HCC cell lines with high (MHCC97H) and low (MHCC97L) metastatic potential was compared. The results showed that MHCC97L was more responsive than MHCC97H to the cytotoxic effect of DHA than MHCC97H. RT-PCR and Western blot analysis of cyclooxygenase-2 (COX-2), a limiting enzyme in prostaoids synthesis, indicated that the anticancer effect of DHA is partly related to the prostaglandins pathway. Bivariate flow cytometric analysis of cell cycle kinetics with bromodeoxyuridine (BrdU) pulse labeling indicated that DHA prolonged the S-phase duration (T ) of MHCC97L cells via G /G phase cells arrest. Measurement of cyclin s 0 1 E/Cdk2 and cyclin A/Cdk2 helped to confirm that the cell cycle control checkpoint of DHA was at the G /S transition. -i- In part two, the influence of olive oil, an integral ingredient of the Mediterranean diet, on human liver cancer was tested in an orthotopic xenograft mice model. Chronic feeding of a 20% (wt/wt) olive oil-enriched diet significantly reduced the tumor volume and intrahepatic metastasis incidence of HCC in nude mice as compared with the control group fed with normal diet. Affymetrix GeneChip analysis of genes expression revealed that the reduced tumor growth of olive oil is partly associated with the down expression of the insulin-like growth factor 1 (IGF-1)-linked focal adhesion pathway genes, such as IGF-1, met proto-oncogene (Met) and protein kinase C alpha (PRKCA); and the focal adhesion and MAPK cascades that are involve in cell migration and growth factor signaling. The slight decrease in p38 MAPK expression may contribute to the decreased cancer cells invasion to the adjacent tissue. The increased expression of the c-Jun N-terminal kinase (JNK) candidates, such as mitogen-activated protein kinase kinase kinase 1 (MAP3K1), mitogen-activated protein kinase kinase 7 (MAP2K7) and c-Jun may be associated with the onset of cell cycle delay and/or induction of apoptosis. In summary, this study is the first to describe the cell cycle effects of DHA on HCC. The data suggest that the therapeutic potential of DHA is dependent on the metastatic potential of the liver cancers. This study also provides the first evidence that olive oil can suppress liver tumor growth and invasiveness. -ii- DOI: 10.5353/th_b3970734 Subjects: Fatty acidsMetastasisLiver - Cancer