J 2018

Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells

LO RE, Oriana, Concetta PANEBIANCO, Stefania PORTO, Carlo CERVI, Francesca RAPPA et. al.

Basic information

Original name

Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells

Authors

LO RE, Oriana (380 Italy, belonging to the institution), Concetta PANEBIANCO (380 Italy), Stefania PORTO (380 Italy), Carlo CERVI (826 United Kingdom of Great Britain and Northern Ireland), Francesca RAPPA (380 Italy), Stefano DI BIASE (840 United States of America), Michele CARAGLIA (840 United States of America), Valerio PAZIENZA (380 Italy) and Manlio VINCIGUERRA (826 United Kingdom of Great Britain and Northern Ireland, guarantor)

Edition

Journal of cellular physiology, HOBOKEN, Liss,a.r, 2018, 0021-9541

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10601 Cell biology

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

Impact factor

Impact factor: 4.522

RIV identification code

RIV/00216224:14110/18:00106866

Organization unit

Faculty of Medicine

DOI

UT WoS

000414593500043

Keywords in English

fasting; hepatic stellate cells; hepatocellular carcinoma; Sorafenib

Tags

Tags

International impact, Reviewed
Změněno: 26/4/2019 17:35, Soňa Böhmová

Abstract

V originále

Hepatocellular carcinoma (HCC) has a poor outcome. Most HCCs develop in the context of liver fibrosis and cirrhosis caused by chronic inflammation. Short-term fasting approaches enhance the activity of chemotherapy in preclinical cancer models, other than HCC. Multi-tyrosine kinase inhibitor Sorafenib is the mainstay of treatment in HCC. However, its benefit is frequently short-lived. Whether fasting can alleviate liver fibrosis and whether combining fasting with Sorafenib is beneficial remains unknown. A 24hr fasting (2% serum, 0.1% glucose)-induced changes on human hepatic stellate cells (HSC) LX-2 proliferation/viability/cell cycle were assessed by MTT and flow cytometry. Expression of lypolysaccharide (LPS)-induced activation markers (vimentin, SMA) was evaluated by qPCR and immunoblotting. Liver fibrosis and inflammation were evaluated in a mouse model of steatohepatitis exposed to cycles of fasting, by histological and biochemical analyses. A 24hr fasting-induced changes were also analyzed on the proliferation/viability/glucose uptake of human HCC cells exposed to Sorafenib. An expression panel of genes involved in survival, inflammation, and metabolism was examined by qPCR in HCC cells exposed to fasting and/or Sorafenib. Fasting decreased the proliferation and the activation of HSC. Repeated cycles of short term starvation were safe in mice but did not improve fibrosis. Fasting synergized with Sorafenib in hampering HCC cell growth and glucose uptake. Finally, fasting normalized the expression levels of genes which are commonly altered by Sorafenib in HCC cells. Fasting or fasting-mimicking diet diets should be evaluated in preclinical studies as a mean to potentiate the activity of Sorafenib in clinical use.