Artículo
Atorvastatin shows antitumor effect in hepatocellular carcinoma development by inhibiting angiogenesis via TGF-β1/pERK signaling pathway
Deza, Zahira Agustina; Caimi, Giselle Romero; Miret, Noelia Victoria
; Coli, Lucía; Ridruejo, Ezequiel
; Alvarez, Laura
Fecha de publicación:
12/2022
Editorial:
Wiley-liss, div John Wiley & Sons Inc.
Revista:
Molecular Carcinogenesis
ISSN:
0899-1987
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
Hepatocellular carcinoma (HCC) represents 90% of liver tumors. Statins may reduce HCC incidence. Its antitumor activities may be mediated by disrupting several hepatocarcinogenic pathways. To evaluate in vivo and in vitro the antiproliferative and antiangiogenic action of atorvastatin (AT) in the development of HCC as well as its mechanisms of action. In vivo model: hexachlorobenzene (HCB) was used to promote the development of HCC in Balb/C nude mice. Number of hepatic tumor, liver cell proliferation parameters (proliferating cell nuclear antigen, PCNA), angiogenesis, and VEGF levels were analyzed. In vitro model: Hep-G2 and Ea-hy926 cells were used to evaluate the effect of different doses of AT on HCB induced cell proliferation, migration, and vasculogenesis and to analyze proliferative parameters. In vivo: AT prevented liver growth and tumor development and inhibited PCNA, TGF-β1, and pERK levels increase. AT prevented skin blood vessel formation. In vitro, AT prevented cell proliferation and migration as well as tubular formation in the endothelial cell line by inhibiting the MAPK ERK pathway. We were able to demonstrate the potential AT antiproliferative and antiangiogenic effects in an HCC model and the involvement of TGF-β1 and pERK pathways.
Palabras clave:
ANGIOGENESIS
,
ERK
,
HEPATOCELLULAR CARCINOMA
,
STATINS
,
TGF-Β1
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Identificadores
Colecciones
Articulos(CEMIC-CONICET)
Articulos de CENTRO DE EDUCACION MEDICA E INVESTIGACIONES CLINICAS "NORBERTO QUIRNO"
Articulos de CENTRO DE EDUCACION MEDICA E INVESTIGACIONES CLINICAS "NORBERTO QUIRNO"
Citación
Deza, Zahira Agustina; Caimi, Giselle Romero; Miret, Noelia Victoria; Coli, Lucía; Ridruejo, Ezequiel; et al.; Atorvastatin shows antitumor effect in hepatocellular carcinoma development by inhibiting angiogenesis via TGF-β1/pERK signaling pathway; Wiley-liss, div John Wiley & Sons Inc.; Molecular Carcinogenesis; 62; 3; 12-2022; 398-407
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