ArticleClinics (Sao Paulo, Brazil)2012
Synergistic growth inhibition by sorafenib and vitamin K2 in human hepatocellular carcinoma cells.
Article in Clinics (Sao Paulo, Brazil), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 20 citations in OpenAlex.
- Antitumor efficacy and molecular mechanism of lenvatinib combined with vitamin K2 against hepatocellular carcinoma.World journal of surgical oncology · 2026Article
- Vitamin K2 in Health and Disease: A Clinical Perspective.Foods (Basel, Switzerland) · 2024Review
- Vitamin K Contribution to DNA Damage-Advantage or Disadvantage? A Human Health Response.Nutrients · 2022Review
- The Activity of Ten Natural Extracts Combined in a Unique Blend to Maintain Cholesterol Homeostasis-In Vitro Model.International journal of molecular sciences · 2022Article
- Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities.Frontiers in pharmacology · 2022Review
- Protective Effects of Vitamin K Compounds on the Proteomic Profile of Osteoblasts under Oxidative Stress Conditions.Molecules (Basel, Switzerland) · 2020Article
- Research progress on the anticancer effects of vitamin K2.Oncology letters · 2018Review
- Review
- Vitamin K and hepatocellular carcinoma: The basic and clinic.World journal of clinical cases · 2015Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveSorafenib is an oral multikinase inhibitor that has been proven effective as a single-agent therapy in hepatocellular carcinoma, and there is a strong rationale for investigating its use in combination with other agents. Vitamin K2 is nearly non-toxic to humans and has been shown to inhibit the growth of hepatocellular carcinoma. In this study, we evaluated the effects of a combination of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells.
methodsFlow cytometry, 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) and nude mouse xenograft assays were used to examine the effects of sorafenib and vitamin K2 on the growth of hepatocellular carcinoma cells. Western blotting was used to elucidate the possible mechanisms underlying these effects.
resultsAssays for 3-(4,5-dimethyl-2-thiazolyl-2,5-diphenyl-2H-tetrazolium bromide) revealed a strong synergistic growth-inhibitory effect between sorafenib and vitamin K2. Flow cytometry showed an increase in cell cycle arrest and apoptosis after treatment with a combination of these two drugs at low concentrations. Sorafenib-mediated inhibition of extracellular signal-regulated kinase phosphorylation was promoted by vitamin K2, and downregulation of Mcl-1, which is required for sorafenib-induced apoptosis, was observed after combined treatment. Vitamin K2 also attenuated the downregulation of p21 expression induced by sorafenib, which may represent the mechanism by which vitamin K2 promotes the inhibitory effects of sorafenib on cell proliferation. Moreover, the combination of sorafenib and vitamin K2 significantly inhibited the growth of hepatocellular carcinoma xenografts in nude mice.
conclusionsOur results determined that combined treatment with sorafenib and vitamin K2 can work synergistically to inhibit the growth of hepatocellular carcinoma cells. This finding raises the possibility that this combined treatment strategy might be promising as a new therapy against hepatocellular carcinoma, especially for patients with poor liver tolerance.
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