Novel Aapproach to HCC, How to Attenuate CancerousPhenotype?

Background: Growing number's of hepatocellular carcinomaand recurrence frequency have drawn researchers' attention toalternative approaches. The concept of differentiation therapyrelies on inducing differentiation in HCC cells in order to inhibitcancerous phenotype. Hepatocyte Nuclear Factor ۴ alphais the key hepatogenesis transcription factor and its upregulationmay decrease cancerous features by suppressing epithelialmesenchymaltransition. This s tudy aimed to evaluate the effectof conjugated Linoleic acid (CLA) treatment, natural ligand ofHNF۴α, on the proliferation, migration, and invasion capacitiesof HCC cells in vitro.Materials and Method: Sk-Hep-۱ and Hep-۳B cells were treatedwith different doses of CLA or BIM۵۰۷۸ [۱-(۲′-chloro-۵′-nitrobenzenesulfonyl)−۲-methylbenzimidazole], an HNF۴αantagonis t. The expression levels of HNF۴a and EMT relatedgenes, were evaluated and associated to hepatocytic functionalities,migration and colony formation capacities.Results: In both HCC lines, CLA treatment induced HNF۴ɑexpression in parallel to significantly decreased EMT markerlevels, migration, colony formation capacity, and proliferationrate, whereas BIM۵۰۷۸ treatment resulted in the opposite effects.Moreover, CLA supplementation also upregulated ALB,ZO۱, and HNF۴α proteins as well as glycogen s torage capacityin the treated HCC cells.Conclusion: CLA treatment can induce hepatocytic differentiationin HCC cells and attenuates cancerous features. This couldbe as a result of HNF۴a induction and EMT inhibition.

کلیدواژه ها:

Conjugated linoleic acid ، Differentiation therapy ، Epithelial-Mesenchymal Transition ، HNF۴α ligand ، Hepatocellularcarcinoma