Insulin-like Growth Factor 2 mRNA-Binding Protein 1 (IGF2BP1) up regulation by Sorafenib in HepG2 cells. Rolls of sirtuins 1 and 2 (SIRT 1/2).

BUCCI MUÑOZ MARIA, ; SEMENIUK MARIANA; LIVORE VERONICA INES; MOTTINO, ALDO DOMINGO

Congreso; Reunion de Sociedades de Biociencias 2020; 2020

Resistance to sorafenib (Sfb) still remains one of the major cause of treatment failure in Hepatocellular carcinoma (HCC). This con￾dition often involves ABC-transporters upregulation, like multidrug resistance-associated protein 3 (ABCC3), that extrudes Sfb from hepatic cells. IGF2BP1 is an oncoprotein highly expressed in HCC which modulates its target genes by affecting their stability, translat￾ability or localization. In a previous work we showed that IGF2BP1 knockdown results in downregulation of ABCC3 in HepG2 cells and that SIRT1/2 inhibitors suppress Sfb-mediated induction of ABCC3. Aim: To evaluate the effect of Sfb on expression of IGF2BP1 and ABCC3 proteins and potential mediation by SIRT1/2. Methods: EX-527 was used as SIRT1/2 inhibitor. Experimental designs were: I) HepG2 cells were treated with 0.75, 2 and 5 µM Sfb (selected from a previous dose-response curve) for 48 and 72 h. II) HepG2 cells were treated for 72 h with Sfb (2µM), EX-527 (40µM) or both. Re￾sults: All results are expressed as % of control (C) and presented as mean±SD, n=3-6, p