Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) upregulation by sorafenib in HepG2 cells. Role of sirtuin 1 and 2 (SIRT1/2)

BUCCI MUÑOZ MARÍA; SEMENIUK MARIANA; LIVORE, VERÓNICA INÉS; MOTTINO, ALDO DOMINGO; CEBALLOS, MARÍA PAULA; RUIZ, MARÍA LAURA

modalidad virtual

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020. LXV Reunión Científica Anual de SAIC.; 2020

Resistance to sorafenib (Sfb) still remains one of the major causeof treatment failure in Hepatocellular carcinoma (HCC). This conditionoften involves ABC-transporters upregulation, like multidrugresistance-associated protein 3 (ABCC3), that extrudes Sfb fromhepatic cells. IGF2BP1 is an oncoprotein highly expressed in HCCwhich modulates its target genes by affecting their stability, translatabilityor localization. In a previous work we showed that IGF2BP1knockdown results in downregulation of ABCC3 in HepG2 cells andthat SIRT1/2 inhibitors suppress Sfb-mediated induction of ABCC3.Aim: To evaluate the effect of Sfb on expression of IGF2BP1 andABCC3 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 froma previous dose-response curve) for 48 and 72 h. II) HepG2 cellswere treated for 72 h with Sfb (2μM), EX-527 (40μM) or both. Results:All results are expressed as % of control (C) and presentedas mean±SD, n=3-6, p