Background: Nowadays, considering the growing number of liver cancer and failure in aggressive treatments differentiation therapy could be considered as a promising strategy for recur-rence inhibition. Numerous efforts have been made to promote differentiation in dedifferentiated hepatocarcinoma cells. Ac-cordingly, HNF4a as a curtail transcription factor in hepato-cytes, emerge to be a kay player in differentiation induction by mediating EMT-MET process. Enhance of HNF4a expression appeared to decrease invasion in carcinoma cells by suppress-ing
Snail and decreasing EMT markers. The current study aims to address invasiveness in hepatocarcinoma cells after treat-ment by a natural ligand.Materials and Methods: We obtained 3 hepatocellular carcinoma (HCC) cell lines form Royan cell bank. Sk-Hep-1 is selected for the study. Then, these cells treated by CLA and BIM5078, as an 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. The expression level of HNF4a, invasiveness and EMT marker genes were assessed using quantitative real time poly-merase 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 vehicles at applied concentration had no cytotoxic effect on cell survival rate. Orangu test results demonstrated that CLA significantly decreased the cell proliferation rate, whereas BIM5078 increased it. Quantitative RT-PCR results showed that CLA enhances the expression of HNF4a and decrease EMT marker genes. Furthermore, migration and colony formation ability of cancerous cells significantly decreased after treatment with CLA.Conclusion: Our data revealed that CLA can induce well-dif-ferentiation in hepatocarcinoma cells particularly on its migra-tion ability by HNF4a induction.