ArticleCellular oncology (Dordrecht, Netherlands)2018
Strong enhancement by IGF1-R antagonists of hepatocellular carcinoma cell migration inhibition by Sorafenib and/or vitamin K1.
Article in Cellular oncology (Dordrecht, Netherlands), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 23 citations in OpenAlex.
- Identification of a novel platelet-related prognostic model for hepatocellular carcinoma.Discover oncology · 2026Article
- MSP-RON signaling in liver pathobiology and as an emerging therapeutic target: a review of the current evidence.Cell communication and signaling : CCS · 2025Review
- Hepatic IR and IGF1R signaling govern distinct metabolic and carcinogenic processes upon PTEN deficiency in the liver.JHEP reports : innovation in hepatology · 2025Article
- (-)-Epigallocatechin-3-Gallate and Quercetin Inhibit Quiescin Sulfhydryl Oxidase 1 Secretion from Hepatocellular Carcinoma Cells.Antioxidants (Basel, Switzerland) · 2025Article
- Vitamin K Contribution to DNA Damage-Advantage or Disadvantage? A Human Health Response.Nutrients · 2022Review
- Long non-coding RNA small nucleolar RNA host genes: functions and mechanisms in hepatocellular carcinoma.Molecular biology reports · 2022Review
- OSI-906 restores the sensitivity of ovarian clear cell carcinoma to cisplatin by targeting the IGF1R/AKT pathway.Medical oncology (Northwood, London, England) · 2022Article
- Overexpression of BACH1 mediated by IGF2 facilitates hepatocellular carcinoma growth and metastasis via IGF1R and PTK2.Theranostics · 2022Article
- Identification of hub genes associated with obesity-induced hepatocellular carcinoma risk based on integrated bioinformatics analysis.Medical oncology (Northwood, London, England) · 2021Article
- Long Non-Coding RNA SNHG14 Contributes to the Development of Hepatocellular Carcinoma via Sponging miR-217.OncoTargets and therapy · 2020Article
- Microscopic vascular invasion by hepatocellular carcinoma in liver transplant patients.Clinical practice (London, England) · 2020Article
- Article
- Hypo-phosphorylated CD147 promotes migration and invasion of hepatocellular carcinoma cells and predicts a poor prognosis.Cellular oncology (Dordrecht, Netherlands) · 2019Article
- Article
- Targeting CDK9 and MCL-1 by a new CDK9/p-TEFb inhibitor with and without 5-fluorouracil in esophageal adenocarcinoma.Therapeutic advances in medical oncology · 2019Article
- Insulin-like Growth Factor-1 Receptor Dictates Beneficial Effects of Treadmill Training by Regulating Survival and Migration of Neural Stem Cell Grafts in the Injured Spinal Cord.Experimental neurobiology · 2018Article
- Sestrin 2 confers primary resistance to sorafenib by simultaneously activating AKT and AMPK in hepatocellular carcinoma.Cancer medicine · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeEmerging evidence indicates that combining Sorafenib with vitamin K1 (VK1) may result in a synergistic inhibition of hepatocellular carcinoma (HCC) cell migration and proliferation. Despite this synergy, its benefits may be limited due to drug resistance resulting from cross-talk with the tumor microenvironment. Insulin-like growth factor-1 (IGF1) signaling acts as an important modulator of HCC cell growth, motility and drug resistance. Therefore, we aimed to explore the effects of Sorafenib in combination with VK1 and/or IGF1-R antagonists on HCC cells.
methodsScratch wound migration assays were performed to assess the motility of HCC-derived PLC/PRF/5, HLF and Hep3B cells. The synergistic, additive or antagonistic effects of Sorafenib, VK1 and IGF1-R antagonists on HCC cell motility were assessed using CompuSyn software. The effects mediated by these various compounds on HCC cytoskeleton organization were evaluated using DyLight 554 Phalloidin staining. Proliferation and migration-associated signaling pathways were analyzed in PLC/PRF/5 cells using Erk1/2 and Akt activation kits and Western blotting (Mek, JNK, Akt, Paxillin and p38), respectively.
resultsThe effects of the IGF1-R antagonists GSK1838705A and OSI-906 on HCC cell migration inhibition after Sorafenib and/or VK1 administration, individually or in combination, were evaluated. We found a synergistic effect in PLC/PRF/5, HLF and Hep3B cells for combinations of fixed doses of GSK1838705A or OSI-906 together with different doses of Sorafenib and/or VK1. The levels of synergy were found to be stronger at higher Sorafenib and/or VK1 concentrations and lower or absent at lower concentrations, with some variation among the different cell lines tested. In addition, we found that in PLC/PRF/5 and HLF cells IGF1-R blockage strongly enhanced the reduction and redistribution of F-actin induced by Sorafenib and/or VK1 through alterations in the phosphorylation levels of some of the principal proteins involved in the MAPK signaling cascade, which is essential for cell migration.
conclusionsOur results indicate that modulation of the efficacy of Sorafenib through combinations with VK1 and/or IGF1-R antagonists results in synergistic inhibition of HCC cell migration.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.