• Something wrong with this record ?

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

O. Lo Re, C. Panebianco, S. Porto, C. Cervi, F. Rappa, S. Di Biase, M. Caraglia, V. Pazienza, M. Vinciguerra,

. 2018 ; 233 (2) : 1202-1212. [pub] 20170711

Language English Country United States

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc18016625

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 24 hr 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, αSMA) 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 24 hr 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.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc18016625
003      
CZ-PrNML
005      
20180516110750.0
007      
ta
008      
180515s2018 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1002/jcp.25987 $2 doi
035    __
$a (PubMed)28471474
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Lo Re, Oriana $u Center for Translational Medicine (CTM), International Clinical Research Center (ICRC), St. Anne's University Hospital, Brno, Czech Republic. Department of Biology, Masaryk University, Brno, Czech Republic.
245    10
$a Fasting inhibits hepatic stellate cells activation and potentiates anti-cancer activity of Sorafenib in hepatocellular cancer cells / $c O. Lo Re, C. Panebianco, S. Porto, C. Cervi, F. Rappa, S. Di Biase, M. Caraglia, V. Pazienza, M. Vinciguerra,
520    9_
$a 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 24 hr 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, αSMA) 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 24 hr 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.
650    _2
$a zvířata $7 D000818
650    _2
$a protinádorové látky $x farmakologie $7 D000970
650    _2
$a hepatocelulární karcinom $x farmakoterapie $x genetika $x metabolismus $x patologie $7 D006528
650    _2
$a proliferace buněk $x účinky léků $7 D049109
650    _2
$a vztah mezi dávkou a účinkem léčiva $7 D004305
650    _2
$a omezení příjmu potravy $x metabolismus $7 D005215
650    _2
$a regulace genové exprese u nádorů $x účinky léků $7 D015972
650    _2
$a glukosa $x metabolismus $7 D005947
650    _2
$a buňky Hep G2 $7 D056945
650    _2
$a jaterní hvězdicovité buňky $x účinky léků $x metabolismus $x patologie $7 D055166
650    _2
$a lidé $7 D006801
650    _2
$a lipopolysacharidy $x farmakologie $7 D008070
650    _2
$a experimentální cirhóza jater $x metabolismus $x patologie $7 D008106
650    _2
$a nádory jater $x farmakoterapie $x genetika $x metabolismus $x patologie $7 D008113
650    _2
$a myši inbrední C57BL $7 D008810
650    _2
$a niacinamid $x analogy a deriváty $x farmakologie $7 D009536
650    _2
$a nealkoholová steatóza jater $x metabolismus $x patologie $7 D065626
650    _2
$a fenylmočovinové sloučeniny $x farmakologie $7 D010671
650    _2
$a časové faktory $7 D013997
655    _2
$a časopisecké články $7 D016428
700    1_
$a Panebianco, Concetta $u Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
700    1_
$a Porto, Stefania $u Department of Biochemistry, Biophysics and General Pathology, University of Campania Luigi Vanvitelli, Naples, Italy. Institute for Liver and Digestive Health, University College London (UCL), Royal Free Hospital, London, UK.
700    1_
$a Cervi, Carlo $u Institute for Liver and Digestive Health, University College London (UCL), Royal Free Hospital, London, UK.
700    1_
$a Rappa, Francesca $u Department of Experimental Biomedicine and Clinical Neurosciences, Section of Human Anatomy, University of Palermo, Palermo, Italy. Euro-Mediterranean Institute of Science and Technology (IEMEST), Palermo, Italy.
700    1_
$a Di Biase, Stefano $u Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles (UCLA), California.
700    1_
$a Caraglia, Michele $u Department of Biochemistry, Biophysics and General Pathology, University of Campania Luigi Vanvitelli, Naples, Italy. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, Pennsylvania. Department of Medicine, Surgery and Neuroscience, University of Siena, Siena, Italy.
700    1_
$a Pazienza, Valerio $u Gastroenterology Unit, IRCCS "Casa Sollievo della Sofferenza" Hospital, San Giovanni Rotondo, Italy.
700    1_
$a Vinciguerra, Manlio $u Center for Translational Medicine (CTM), International Clinical Research Center (ICRC), St. Anne's University Hospital, Brno, Czech Republic. Institute for Liver and Digestive Health, University College London (UCL), Royal Free Hospital, London, UK.
773    0_
$w MED00009981 $t Journal of cellular physiology $x 1097-4652 $g Roč. 233, č. 2 (2018), s. 1202-1212
856    41
$u https://pubmed.ncbi.nlm.nih.gov/28471474 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20180515 $b ABA008
991    __
$a 20180516110925 $b ABA008
999    __
$a ok $b bmc $g 1300249 $s 1013465
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2018 $b 233 $c 2 $d 1202-1212 $e 20170711 $i 1097-4652 $m Journal of cellular physiology $n J Cell Physiol $x MED00009981
LZP    __
$a Pubmed-20180515

Find record

Citation metrics

Archiving options