prikaz prve stranice dokumenta Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling
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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. https://doi.org/10.1016/j.bbrc.2017.04.100
Grbčić, Petra; Tomljanović, Ivana; Klobučar, Marko; Kraljević Pavelić, Sandra; Lučin, Ksenija; Sedić, Mirela

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Grbčić, P., Tomljanović, I., Klobučar, M., Kraljević Pavelić, S., Lučin, K. i Sedić, M. (2017). 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. (4), 782-788. doi: 10.1016/j.bbrc.2017.04.100

Grbčić, Petra, et al. "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, vol. 487, br. 4, 2017, str. 782-788. https://doi.org/10.1016/j.bbrc.2017.04.100

Grbčić, Petra, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin i Mirela Sedić. "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, br. 4 (2017): 782-788. https://doi.org/10.1016/j.bbrc.2017.04.100

Grbčić, P., et al. (2017) '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(4), str. 782-788. doi: 10.1016/j.bbrc.2017.04.100

Grbčić P, Tomljanović I, Klobučar M, Kraljević Pavelić S, Lučin K, Sedić M. 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 [Internet]. 2017. [pristupljeno 22.10.2024.];487(4):782-788. doi: 10.1016/j.bbrc.2017.04.100

P. Grbčić, I. Tomljanović, M. Klobučar, S. Kraljević Pavelić, K. Lučin i M. Sedić, "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, vol. 487, br. 4, str. 782-788, 2017. [Online]. Dostupno na: https://urn.nsk.hr/urn:nbn:hr:184:898401. [Citirano: 22.10.2024.]

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Podaci o radu
Naslov (engleski)Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling
AutorPetra Grbčić
MBZ: 370433
AutorIvana Tomljanović
MBZ: 370455
AutorMarko Klobučar
MBZ: 340744
AutorSandra Kraljević Pavelić
MBZ: 254965
AutorKsenija Lučin
AutorMirela Sedić
MBZ: 258565
Autorova ustanovaSveučilište u Rijeci
Medicinski fakultet
(Katedra za opću patologiju i patološku anatomiju)
Znanstveno / umjetničko
područje, polje i grana		BIOMEDICINA I ZDRAVSTVO
Kliničke medicinske znanosti
Znanstveno / umjetničko
područje, polje i grana		BIOTEHNIČKE ZNANOSTI
Biotehnologija
Sažetak (engleski)
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.
Ključne riječi (engleski)
Jezikengleski
Vrsta publikacijeZnanstveni rad - Izvorni znanstveni rad
Status objaveObjavljen
Vrsta recenzijeRecenziran - međunarodna recenzija
Verzija publikacijeObjavljena verzija rada (izdavačev PDF)
Naslov časopisaBiochemical and biophysical research communications
Brojčani podacivol. 487, br. 4, str. 782-788
p-ISSN0006-291X
DOIhttps://doi.org/10.1016/j.bbrc.2017.04.100
URN:NBNurn:nbn:hr:184:898401
Datum objave publikacije2017
URL dokumentahttp://bib.irb.hr/882345
Vrsta resursaTekst
Prava pristupaZatvoreni pristup
Uvjeti korištenjaIkona licence Zaštićeno autorskim pravom.
Datum i vrijeme pohrane2022-02-17 12:10:28