P-49 EFFECT OF STATINS IN REVERSING CELL GROWTH DYSREGULATION IN THE EARLY STAGES OF HEPATOCARCINOGENESIS

Abstract

Conflict of interest: No Introduction and Objectives: Hepatocellular carcinoma (HCC) is the most common primary liver tumor and the fifth leading cause of cancer death. Hexachlorobenzene (HCB) is an environmental pollutant and endocrine disruptor. It plays a role in hepatocarcinogenesis by promoting angiogenesis and cell proliferation, partly by altering thyroid hormones, regulators of the cell cycle.We previously demonstrated that HCB deregulates liver growth, involving TGF-β1 and triiodothyronine (T3); and that Atorvastatin (AT) prevents these effects. Objective: To evaluate the capacity of AT to reverse the effects generated by HCB in the early stages of HCC development. Patients / Materials and Methods: We analyzed the effect of HCB (5μM) with/without AT (20μM) in Huh-7 cell line on 1-(PCNA), 2-(caspase-3 and cytochrome-c), 3-(TGF-β1), 4-(Cox-2); by western blot; 5- T3-generating enzyme (Deiodinase I); RT-PCR; 6-cell migration, wound technique; 7-number of colonies. We evaluated the reversal effect of AT on the previously mentioned parameters. Results and Discussion: HCB increased cell proliferation and migration (PCNA levels 38%, p <0.01), cell migration (47%, p <0.05) and number of colonies (44%, p <0.05); induced apoptosis (Cytochrome-c 30%, p <0.01, and caspase-3 27%, p <0.05); induced inflammation (TGF-β1 41%, p <0.01, and Cox-2 28%, p <0.05) when compared to the control. In addition, decreased T3 levels by decreasing DI (28%, p <0.05). Atorvastatin reversed these effects on every parameter studied, reaching control values. Conclusions: Atorvastatin administration, in addition to prevention, can reverse proliferation, migration, inflammation, and apoptosis in our model, potentially reversing the deregulation of cell growth in the early stages of hepatocarcinogenesis. In addition, AT restores DI activity, potentially balancing thyroid metabolism.