Ramucirumab and GSK1838705A enhance the inhibitory effects of low concentration sorafenib and regorafenib combination on HCC cell growth and motility

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dc.authorscopusid57190086878
dc.authorscopusid36437549800
dc.authorscopusid7801589850
dc.authorscopusid57202788086
dc.authorscopusid7004822293
dc.authorscopusid57217614267
dc.contributor.authorD’Alessandro R.
dc.contributor.authorRefolo M.G.
dc.contributor.authorIacovazzi P.A.
dc.contributor.authorPesole P.L.
dc.contributor.authorMessa C.
dc.contributor.authorCarr B.I.
dc.date.accessioned2024-08-04T20:03:31Z
dc.date.available2024-08-04T20:03:31Z
dc.date.issued2019
dc.departmentİnönü Üniversitesien_US
dc.description.abstractSeveral new multikinase inhibitors have recently been introduced into clinical practice for hepatocellular carcinoma (HCC) therapy. Small increases in survival were reported as well as considerable toxicity. There is thus a need for effective therapies with lower toxicities. We examined whether a combination of sorafenib and regorafenib might also be effective at very low concentrations, with resulting potential for lessened clinical toxicity. MTT test, clonogenic assay, Ki67 staining and cell cycle analysis were assessed for cell proliferation and Annexin V and western blotting analysis relative to the expression of cleaved Caspase-3 and BID for cell apoptosis. In these experimental conditions cell growth and migration were potently inhibited and apoptosis induced even in HCC cells producing high alpha fetoprotein (AFP) levels (clinically worse prognosis). The combination also inhibited levels of the two HCC biomarkers, AFP and des gamma carboxy prothrombin (DCP). Additional inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR) or Insulin-like Growth Factor 1 Receptor (IGF1R) enhanced effects on AFP and DCP levels, cell growth inhibition and MAPK and PI3K/Akt signaling inhibition due to sorafenib/regorafenib combination. These combinations have the potential for decreased toxicity while simultaneously enhancing therapeutic effects. This potential decrease in toxicity is being explored in ongoing studies. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.en_US
dc.description.sponsorship6/2018; National Institutes of Health, NIH: CA 82723en_US
dc.description.sponsorshipFunding: This research was supported by Italian Ministry of Public Health (n.6/2018) and in part by NIH grant CA 82723 (B.I.C).en_US
dc.identifier.doi10.3390/cancers11060787
dc.identifier.issn2072-6694
dc.identifier.issue6en_US
dc.identifier.scopus2-s2.0-85070564381en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.urihttps://doi.org/10.3390/cancers11060787
dc.identifier.urihttps://hdl.handle.net/11616/91879
dc.identifier.volume11en_US
dc.indekslendigikaynakScopusen_US
dc.language.isoenen_US
dc.publisherMDPI AGen_US
dc.relation.ispartofCancersen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCombination therapyen_US
dc.subjectDes-?-carboxyprothrombinen_US
dc.subjectInsulin-like growth factor 1 receptoren_US
dc.subjectMulti-kinase inhibitorsen_US
dc.subjectSynergismen_US
dc.subjectVascular endothelial growth factor receptoren_US
dc.subject? fetoproteinen_US
dc.titleRamucirumab and GSK1838705A enhance the inhibitory effects of low concentration sorafenib and regorafenib combination on HCC cell growth and motilityen_US
dc.typeArticleen_US

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