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

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.

Základní údaje

Originální název

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

Autoři

LO RE, Oriana (380 Itálie, domácí), Concetta PANEBIANCO (380 Itálie), Stefania PORTO (380 Itálie), Carlo CERVI (826 Velká Británie a Severní Irsko), Francesca RAPPA (380 Itálie), Stefano DI BIASE (840 Spojené státy), Michele CARAGLIA (840 Spojené státy), Valerio PAZIENZA (380 Itálie) a Manlio VINCIGUERRA (826 Velká Británie a Severní Irsko, garant)

Vydání

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

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10601 Cell biology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 4.522

Kód RIV

RIV/00216224:14110/18:00106866

Organizační jednotka

Lékařská fakulta

DOI

http://dx.doi.org/10.1002/jcp.25987

UT WoS

000414593500043

Klíčová slova anglicky

fasting; hepatic stellate cells; hepatocellular carcinoma; Sorafenib

Štítky

14110513, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 26. 4. 2019 17:35, Soňa Böhmová

Anotace

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.

Citovat

LO RE, Oriana, Concetta PANEBIANCO, Stefania PORTO, Carlo CERVI, Francesca RAPPA, Stefano DI BIASE, Michele CARAGLIA, Valerio PAZIENZA a 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, roč. 233, č. 2, s. 1202-1212. ISSN 0021-9541. Dostupné z: https://dx.doi.org/10.1002/jcp.25987.

@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 a 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, roč.~233, č.~2, s.~1202-1212. ISSN~0021-9541. Dostupné z: https://dx.doi.org/10.1002/jcp.25987.

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