Napredna pretraga

Pregled bibliografske jedinice broj: 882345

Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling


Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko; Kraljević Pavelić, Sandra; Lučin, Ksenija; Sedić, Mirela
Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling // Biochemical and biophysical research communications, 487 (2017), 4; 782-788 doi:10.1016/j.bbrc.2017.04.100 (međunarodna recenzija, članak, znanstveni)


Naslov
Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling

Autori
Grbčić, Petra ; Tomljanović, Ivana ; Klobučar, Marko ; Kraljević Pavelić, Sandra ; Lučin, Ksenija ; Sedić, Mirela

Izvornik
Biochemical and biophysical research communications (0006-291X) 487 (2017), 4; 782-788

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Hepatocellular carcinoma ; Sphingosine kinase ; SKI-II ; Osteopontin ; IGF-1R ; SIRT1

Sažetak
Hepatocellular carcinoma (HCC) represents the third leading cause of cancer-related deaths globally. Although 5-Fluorouracil (5-FU) is used as the first choice treatment for advanced HCC, it exerts poor efficacy and is associated with acquired and intrinsic resistance. Sphingosine kinases (Sphk) 1 and 2 play tumour-promoting roles in different cancer types including HCC and thus represent promising pharmacological targets. In the present study, we have investigated for the first time the anticancer efficacy and underlying molecular mechanisms of combined administration of 5-FU and dual Sphk1/Sphk2 inhibitor SKI-II (4-[[4-(4-chlorophenyl)-1, 3-thiazol-2-yl]amino]phenol) in HepG2 hepatocellular carcinoma cells. Here, we report that co-administration of 5-FU and SKI-II at low sub-toxic concentrations of 20 μM and 5 μM, respectively, synergistically inhibit cell proliferation, markedly reduce cell migration and the clonogenic survival, and increase apoptosis induction in HepG2 cells. Additional Western blot analyses have shown that possible mechanisms underlying enhanced sensitivity to 5-FU induced by dual Sphk 1/2 inhibition could include abrogation of FAK-regulated IGF-1R activity and down-regulation of osteopontin expression culminating in the inhibition of NF-κB activity and its downstream signalling mediated by sirtuin 1 and p38 MAPK. Our results clearly show that pharmacological blockade of both Sphk isoforms represents a promising strategy to boost the anti-tumour efficacy of 5-FU and provide a rationale for further in vivo studies into the possible use of SKI-II inhibitor as an adjunct to 5-FU treatment in HCC.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

Napomena
University of Rijeka: 13.11.1.1.11. 13.11.2.1.12. 13.06.1.2.21

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Citati