Background: Nowadays considering the growing number of liver neoplasia and lack of failure in effective treatment, , differentiation therapy is considered as a promising strategy for inhibition of recurrence. Numerous efforts have been made to promote differentiation in cancerous cells. HNF4a as a curtail transcription factor in hepatocytes, emerge to be a kay conductor in differentiation by mediating EMT-MET process. Enhancement of HNF4a expression appeared to decrease invasion in carcinoma cells by suppressing Snail and decreasing EMT markers. Conjugated Linoleic acid (CLA) is an essential fatty acid has been identified as a potential anti-obesogenic and anti-carcinogenic agent. It is also known as a natural ligand of HNF4a

Material and Method: The Sk-Hep-1 cells treated by CLA and BIM5078, antagonist of HNF4a, as a negative control. The effects of CLA on cellular behavior were measured by assessing cell viability and proliferation rate at different time points using Orangu test. The expression level of HNF4a, invasiveness and EMT marker genes were assessed by quantitative real time polymerase change reaction (qRT-PCR). Moreover, migration and colony formation ability were assessed by scratch and colony formation assay.

Results: MTT results showed that CLA and BIM5078 and their vehicle at applied concentration had no cytotoxic effect on cell survival rate. Orangu test results demonstrated that CLA significantly decreased the cell proliferation whereas BIM5078 increased it. qRT-PCR results showed CLA enhances the expression of HNF4a and decrease EMT marker genes also induced the level of ALB, E-CAD and CYP3-A4 but BIM5078 acted in opposite direction. Furthermore, Migration and colony formation ability significantly had decreased by CLA whereas BIM5078 increased them.

Conclusion: Finally, all of our data showed that CLA promote well-differentiation in hepatocarcinoma cell especially in its migration ability by HNF4a induction via EMT inhibition.