ArticleOncotarget2016
Des-gamma-carboxy prothrombin antagonizes the effects of Sorafenib on human hepatocellular carcinoma through activation of the Raf/MEK/ERK and PI3K/Akt/mTOR signaling pathways.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- The prognostic value of protein induced by vitamin K absence or antagonist-II in hepatocellular carcinoma patients undergoing surgical resection.European journal of gastroenterology & hepatology · 2026Article
- Cinobufacini Inhibits Survival and Metastasis of Hepatocellular Carcinoma via c-Met Signaling Pathway.Chinese journal of integrative medicine · 2025Article
- Resveratrol liposomes reverse sorafenib resistance in renal cell carcinoma models by modulating PI3K-AKT-mTOR and VHL-HIF signaling pathways.International journal of pharmaceutics: X · 2024Article
- The effects of Sorafenib and Natural killer cell co-injection in combinational treatment of hepatocellular carcinoma; an in vivo approach.Pharmacological reports : PR · 2022Article
- MiR-29a Curbs Hepatocellular Carcinoma Incidence via Targeting ofInternational journal of molecular sciences · 2022Article
- Pulmonary Mesenchymal Stem Cells in Mild Cases of COVID-19 Are Dedicated to Proliferation; In Severe Cases, They Control Inflammation, Make Cell Dispersion, and Tissue Regeneration.Frontiers in immunology · 2021Article
- β-arrestin2 regulating β2-adrenergic receptor signaling in hepatic stellate cells contributes to hepatocellular carcinoma progression.Journal of Cancer · 2021Article
- Promising anticancer therapy: combination of immune checkpoint inhibitors and molecular-targeted agents.Hepatobiliary surgery and nutrition · 2020Article
- SNGH16 regulates cell autophagy to promote Sorafenib Resistance through suppressing miR-23b-3p via sponging EGR1 in hepatocellular carcinoma.Cancer medicine · 2020Article
- mTOR and ERK regulate VKORC1 expression in both hepatoma cells and hepatocytes which influence blood coagulation.Clinical and experimental medicine · 2019Article
- Capsaicin and sorafenib combination treatment exerts synergistic anti‑hepatocellular carcinoma activity by suppressing EGFR and PI3K/Akt/mTOR signaling.Oncology reports · 2018Article
- Angiopoietin-like protein 3 blocks nuclear import of FAK and contributes to sorafenib response.British journal of cancer · 2018Article
- Inhibition of HSP90 sensitizes a novel Raf/ERK dual inhibitor CY-9d in triple-negative breast cancer cells.Oncotarget · 2017Article
- MicroRNA-1296 inhibits metastasis and epithelial-mesenchymal transition of hepatocellular carcinoma by targeting SRPK1-mediated PI3K/AKT pathway.Molecular cancer · 2017Article
- Lymphocyte-specific protein 1 inhibits the growth of hepatocellular carcinoma by suppressing ERK1/2 phosphorylation.FEBS open bio · 2016Article
- Clinical significance of mitofusin-2 and its signaling pathways in hepatocellular carcinoma.World journal of surgical oncology · 2016Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite significant progress, advanced hepatocellular carcinoma (HCC) remains an incurable disease, and the overall efficacy of targeted therapy by Sorafenib remains moderate. We hypothesized that DCP (des-gamma-carboxy prothrombin), a prothrombin precursor produced in HCC, might be one of the reasons linked to the low efficacy of Sorafenib. We evaluated the efficacy of Sorafenib in HLE and SK-Hep cells, both of which are known DCP-negative HCC cell lines. In the absence of DCP, Sorafenib effectively inhibited the growth of HCC and induced cancer cell apoptosis. In the presence of DCP, HCC was resistant to Sorafenib-induced inhibition and apoptosis, as determined by in vitro assays and in mice xenografted with HLE cells. Molecular analysis of HLE xenografted-nude mice showed that DCP activates the transduction of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR cascades. DCP might stimulate the formation of compensatory feedback loops in the intricately connected signaling pathways when kinases are targeted by Sorafenib. Our results indicate that DCP antagonizes the inhibitory effects of Sorafenib on HCC through activation of the Ras/Raf/MEK/ERK and Ras/PI3K/Akt/mTOR signaling pathways. Taken together, our findings define a DCP-mediated mechanism of inhibition of Sorafenib in HCC, which is critical for targeting therapy in advanced HCC.
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