| LO RE, Oriana, Concetta PANEBIANCO, Stefania PORTO, Carlo CERVI, Francesca RAPPA, Stefano DI BIASE, Michele CARAGLIA, Valerio PAZIENZA and Manlio VINCIGUERRA. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells. Journal of cellular physiology. HOBOKEN: Liss,a.r, 2018, vol. 233, No 2, p. 1202-1212. ISSN 0021-9541. Available from: https://dx.doi.org/10.1002/jcp.25987. |
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@article{1526425,
author = {Lo Re, Oriana and Panebianco, Concetta and Porto, Stefania and Cervi, Carlo and Rappa, Francesca and Di Biase, Stefano and Caraglia, Michele and Pazienza, Valerio and Vinciguerra, Manlio},
article_location = {HOBOKEN},
article_number = {2},
doi = {http://dx.doi.org/10.1002/jcp.25987},
keywords = {fasting; hepatic stellate cells; hepatocellular carcinoma; Sorafenib},
language = {eng},
issn = {0021-9541},
journal = {Journal of cellular physiology},
title = {Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells},
volume = {233},
year = {2018}
}
TY - JOUR
ID - 1526425
AU - Lo Re, Oriana - Panebianco, Concetta - Porto, Stefania - Cervi, Carlo - Rappa, Francesca - Di Biase, Stefano - Caraglia, Michele - Pazienza, Valerio - Vinciguerra, Manlio
PY - 2018
TI - Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells
JF - Journal of cellular physiology
VL - 233
IS - 2
SP - 1202-1212
EP - 1202-1212
PB - Liss,a.r
SN - 00219541
KW - fasting
KW - hepatic stellate cells
KW - hepatocellular carcinoma
KW - Sorafenib
N2 - 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.
ER -
LO RE, Oriana, Concetta PANEBIANCO, Stefania PORTO, Carlo CERVI, Francesca RAPPA, Stefano DI BIASE, Michele CARAGLIA, Valerio PAZIENZA and Manlio VINCIGUERRA. Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells. \textit{Journal of cellular physiology}. HOBOKEN: Liss,a.r, 2018, vol.~233, No~2, p.~1202-1212. ISSN~0021-9541. Available from: https://dx.doi.org/10.1002/jcp.25987.
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