New therapeutic strategy for hepatocellular carcinoma: bioinformatic identificacion and pharmacological inhibition of Rac1 GTPasa

FIORE E; BAYO JM; DOMÍNGUEZ LM; CANTERO MJ; CIARLANTINI M ; MALVICINI M; ATORRASAGASTI C; GARCIA M; COMIN MJ; MAZZOLINI G

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencia (SAIC SAI SAFIS); 2020

Introduction: Tumors take advantage of the deregulation of RHO GTPases to acquire several cancer hallmarks. We aimed to identify and target deregulated RHO family members in human hepatocellular carcinoma (HCC). Methodology: Expression deregulation, clinical prognosis, and transcription programs relevant to HCC was studied employing 3 public datasets (TCGA, ICGC andGSE14520). The therapeutic potential of RAC1 inhibitors was study in vitro by MTT, apoptosis (Propidium iodide) and cell cycle (Annexin-V) in HCC cell line; and in vivo in a subcutaneous (sc) HuH7 or orthotopic Hepa129 tumor mice models. RNA-Seq analysis of RAC1 inhibition on HuH7 cells was assessed and data correlated with the HCC datasets to characterize the underlying mechanism. The therapeutic effect of RAC1 inhibition on liver fibrosis was evaluated on Thioacetamide experimental model (600 mg/Kg/week). Results: Among RHO family, only RAC1 is upregulated (paired t‑test, p