NOVEL ROLES OF MTP ON CANCER DEVELOPMENT, CELL SURVIVAL AND MIGRATION

LUCCI A; CEBALLOS M P; QUIROGA A D; COMANZO C G; LORENZETTI FLORENCIA; ALVAREZ M L; VERA MC; FERRETTI A

Paraná

Congreso; LIV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular (SAIB); 2018

Microsomal triacylglycerol transfer protein (MTP) locates in the lumen of the endoplasmic reticulum and participates in the secretion of lipids from the liver as very low density lipoproteins. There is evidence that MTP might be involved in other cellular processes, including the pathogenesis of different diseases; however, no studies were performed yet to evaluate if MTP plays a role in cancer. Therefore, the objective of this work was to study the participation of MTP on liver cancer. First, we assesed MTP mRNA and protein expressions in livers from rats subjected to a 2-phase model (initiation-promotion ? IP) of chemical hepatocarcinogenesis. We observed an increase in MTP expression in IP group vs. control (C) group. Then, we analyze MTP protein expression in C57Bl/6 mice euthanized 6 (early stage) or 40 weeks (late stage) after hepatocarcinogenic treatment. Liver MTP protein levels were significantly higher on early stages, compared to C animals, whereas differences in protein expression were less evident between both groups on the late stages. Additionally, we studied the effects of an MTP inhibitor (Lomitapide) on hepatocellular carcinoma cell lines Huh7 and HepG2. MTT assay showed that Lomitapide significantly reduced cellular viability in a dose-dependent manner compared to untreated cells in both cell lines. This result was confirmed by clonogenic survival assay. Wound healing assay showed that also the cellular migration was significantly reduced in a dose-dependent manner upon Lomitapide treatment. Conclusion: although preliminary our results demonstrate a novel role for MTP on cancer development, cell survival and migration.