ArticleAmerican journal of translational research2017
GC7 blocks epithelial-mesenchymal transition and reverses hypoxia-induced chemotherapy resistance in hepatocellular carcinoma cells.
Article in American journal of translational research, 2017. 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, 23 citations in OpenAlex.
- Overcoming resistance to arginine deprivation therapy using GC7 in pleural mesothelioma.iScience · 2025Article
- An experimental target-based platform in yeast for screening Plasmodium vivax deoxyhypusine synthase inhibitors.PLoS neglected tropical diseases · 2024Article
- Hypoxia-Inducible Factor-Dependent and Independent Mechanisms Underlying Chemoresistance of Hypoxic Cancer Cells.Cancers · 2024Review
- Translation factor accelerating peptide bond formation on the ribosome: EF-P and eIF5A as entropic catalysts and a potential drug targets.BBA advances · 2023Article
- Metformin administration is associated with enhanced response to transarterial chemoembolization for hepatocellular carcinoma in type 2 diabetes patients.Scientific reports · 2022Article
- Eukaryotic initiation factor 5A2 mediates hypoxia-induced autophagy and cisplatin resistance.Cell death & disease · 2022Article
- Hypusinated EIF5A as a feasible drug target for Advanced Medicinal Therapies in the treatment of pathogenic parasites and therapy-resistant tumors.Amino acids · 2022Review
- Role of eIF5A in Mitochondrial Function.International journal of molecular sciences · 2022Review
- Article
- EIF5A2 controls ovarian tumor growth and metastasis by promoting epithelial to mesenchymal transition via the TGFβ pathway.Cell & bioscience · 2021Article
- Encapsulating TGF-β1 Inhibitory Peptides P17 and P144 as a Promising Strategy to Facilitate Their Dissolution and to Improve Their Functionalization.Pharmaceutics · 2020Article
- Overexpression of microRNA-9 enhances cisplatin sensitivity in hepatocellular carcinoma by regulating EIF5A2-mediated epithelial-mesenchymal transition.International journal of biological sciences · 2020Article
- Hypoxia‑inducible factors in hepatocellular carcinoma (Review).Oncology reports · 2020Review
- MicroRNA-383 inhibits doxorubicin resistance in hepatocellular carcinoma by targeting eukaryotic translation initiation factor 5A2.Journal of cellular and molecular medicine · 2019Article
- Liver Cancer Cell Lines Treated with Doxorubicin under Normoxia and Hypoxia: Cell Viability and Oncologic Protein Profile.Cancers · 2019Article
- Eukaryotic initiation factor 5A2 and human digestive system neoplasms.World journal of gastrointestinal oncology · 2019Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is common in solid tumors and results in the activation of hypoxia-response genes. Hypoxia-inducible factor-1α (HIF-1α) is thought to reflect major cellular adaptation to hypoxia and contributes to chemoresistance in various tumors including hepatocellular carcinoma (HCC). N1-guanyl-1,7-diaminoheptane (GC7) is an inhibitor which suppresses the active eukaryotic translation initiation factor 5A-2 (eIF5A2), preventing epithelial-mesenchymal transition (EMT) in chemoresistance. In this study, we investigated the role of GC7 in the therapeutic effect of doxorubicin in hypoxia in HCC. We utilized four types of HCC cell line (Huh7, Hep3B, SNU387 and SNU449) in this study. Western blot and immunofluorescence were used to detect expression of epithelial/mesenchymal markers for EMT evaluation and HIF-1α was knocked down using HIF-1α-siRNA. Hypoxia-induced EMT contributed to doxorubicin chemoresistance in HCC cells. Low concentrations of GC7 sensitized Huh7 and Hep3B to doxorubicin by reversing EMT. Knockdown of HIF-1α attenuated hypoxia-induced EMT and abolished the unique feature of GC7. GC7 enhanced sensitivity to doxorubicin in HCC by reversing hypoxia-induced EMT via the HIF-1α-mediated signaling pathway. We suggest a new method of enhancing cytotoxicity of chemotherapy and improving the long-term survival rate in HCC.
Indexed as
Identifiers
28560008PMC5446540W3022637012What OpenQuestion holds
Registered trials
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.