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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Scientific paper - Original scientific paper
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. & 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, no. 4, 2017, pp. 782-788. https://doi.org/10.1016/j.bbrc.2017.04.100

Grbčić, Petra, Ivana Tomljanović, Marko Klobučar, Sandra Kraljević Pavelić, Ksenija Lučin and 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, no. 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), pp. 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 [cited 2024 November 15];487(4):782-788. doi: 10.1016/j.bbrc.2017.04.100

P. Grbčić, I. Tomljanović, M. Klobučar, S. Kraljević Pavelić, K. Lučin and 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, no. 4, pp. 782-788, 2017. [Online]. Available at: https://urn.nsk.hr/urn:nbn:hr:184:898401. [Accessed: 15 November 2024]

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Metadata
Title (english)Dual sphingosine kinase inhibitor SKI-II enhances sensitivity to 5-fluorouracil in hepatocellular carcinoma cells via suppression of osteopontin and FAK/IGF-1R signalling
AuthorPetra Grbčić
MBZ: 370433
AuthorIvana Tomljanović
MBZ: 370455
AuthorMarko Klobučar
MBZ: 340744
AuthorSandra Kraljević Pavelić
MBZ: 254965
AuthorKsenija Lučin
AuthorMirela Sedić
MBZ: 258565
Author's institutionUniversity of Rijeka
Faculty of Medicine
(Department of General Pathology and Pathological Anatomy)
Scientific / art field,
discipline and subdiscipline		BIOMEDICINE AND HEALTHCARE
Clinical Medical Sciences
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Abstract (english)
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.
Keywords (english)
Languageenglish
Publication typeScientific paper - Original scientific paper
Publication statusPublished
Peer reviewPeer review - international
Publication versionPublished version
Journal titleBiochemical and biophysical research communications
Numberingvol. 487, no. 4, pp. 782-788
p-ISSN0006-291X
DOIhttps://doi.org/10.1016/j.bbrc.2017.04.100
URN:NBNurn:nbn:hr:184:898401
Publication2017
Document URLhttp://bib.irb.hr/882345
Type of resourceText
Access conditionsClosed access
Terms of useLicence In copyright icon
Created on2022-02-17 12:10:28