ArticleCancer & metabolism2023
A feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC.
Article in Cancer & metabolism, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Ginsenoside Rh2 Regulates PI3K/AKT Signaling, Metabolic Pathways, and the Gut Microbiota for Coronary Heart Disease Therapy.International journal of molecular sciences · 2026Article
- Metabolism and Metabolic Reprogramming in Laryngeal Squamous Cell Carcinoma.Biomedicines · 2026Review
- Unraveling regorafenib resistance: metabolic reprogramming, tumor plasticity, and novel approaches to overcome therapy failure.Archives of pharmacal research · 2026Review
- Pleiotropic mechanisms of cancer-associated fibroblast-mediated resistance in hepatocellular carcinoma: emerging therapeutic vulnerabilities and targeting strategies.Cancer gene therapy · 2026Review
- Hispidulin Suppresses Hepatocellular Carcinoma Proliferation by Targeting PI3K-Akt Pathway: A Network Pharmacology and Experimental Validation Study.Journal of hepatocellular carcinoma · 2026Article
- Long non-coding RNA LINC01532 sustains redox homeostasis and accelerates lenvatinib resistance in hepatocellular carcinoma.Journal of advanced research · 2025Article
- AFP promotes cancer multidrug resistance through activating PI3K/Akt/NF-κB signaling pathway.Scientific reports · 2025Article
- Molecular network of metabolic reprogramming and precision diagnosis and treatment of hepatocellular carcinoma.Biomarker research · 2025Review
- Bile acid metabolism and hepatocellular carcinoma: mechanisms of drug resistance and intervention strategies.Precision clinical medicine · 2025Review
- The Pentose Phosphate Pathway: From Mechanisms to Implications for Gastrointestinal Cancers.International journal of molecular sciences · 2025Review
- Proteomic Characterization of Liver Cancer Cells Treated with Clinical Targeted Drugs for Hepatocellular Carcinoma.Biomedicines · 2025Article
- Digital patient modeling identifies predictive biomarkers of regorafenib response in elderly metastatic colorectal cancer.Frontiers in systems biology · 2025Article
- Stemness- and hypoxia-based prognostic stratification index reveals G6PD as a regulator of hypoxia-driven stemness in hepatocellular carcinoma.Frontiers in immunology · 2025Article
- Review
- Glutathione-Dependent Pathways in Cancer Cells.International journal of molecular sciences · 2024Review
- The Cancer Antioxidant Regulation System in Therapeutic Resistance.Antioxidants (Basel, Switzerland) · 2024Review
- Review
- Signaling pathways in liver cancer: pathogenesis and targeted therapy.Molecular biomedicine · 2024Review
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundHepatocellular carcinoma (HCC) is a principal type of liver cancer with high incidence and mortality rates. Regorafenib is a novel oral multikinase inhibitor for second-line therapy for advanced HCC. However, resistance to regorafenib is gradually becoming a dilemma for HCC and the mechanism remains unclear. In this study, we aimed to reveal the metabolic profiles of regorafenib-resistant cells and the key role and mechanism of the most relevant metabolic pathway in regorafenib resistance.
methodsMetabolomics was performed to detect the metabolic alteration between drug-sensitive and regorafenib-resistant cells. Colony formation assay, CCK-8 assay and flow cytometry were applied to observe cell colony formation, cell proliferation and apoptosis, respectively. The protein and mRNA levels were detected by western blot and RT-qPCR. Cell lines of Glucose-6-phosphate dehydrogenase(G6PD) knockdown in regorafenib-resistant cells or G6PD overexpression in HCC cell lines were stably established by lentivirus infection technique. G6PD activity, NADPH level, NADPH/NADP
resultsMetabonomics analysis revealed that pentose phosphate pathway (PPP) was the most relevant metabolic pathway in regorafenib resistance in HCC. Compared with drug-sensitive cells, G6PD enzyme activity, NADPH level and NADPH/NADP
conclusionTaken together, a feedback loop of PPP and PI3K/AKT signal pathway drives regorafenib-resistance in HCC and targeting the feedback loop could be a promising approach to overcome drug resistance.
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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.