ArticleBMC cancer2020
Oxaliplatin resistance is enhanced by saracatinib via upregulation Wnt-ABCG1 signaling in hepatocellular carcinoma.
Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- Cholesterol-Lowering Treatment Blocks Epithelial-Mesenchymal Transition (EMT) Associated Invasiveness and Drug Resistance in Breast and Colorectal Adenocarcinoma Models.Cancer medicine · 2026Article
- Astragalus Polysaccharides Target the Wnt/β-catenin Pathway to Suppress Malignant Behavior in Hepatocellular Carcinoma.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2026Article
- Cancer-associated fibroblast-derived GAS6 increases resistance to chemotherapy through AXL/STAT3/ABCG1 in gastric cancer.British journal of cancer · 2026Article
- Mechanism of ECM Stiffness-Integrin-Hippo-ABCG1 axis in regulating ferroptosis and targeted nanodrug intervention in LUAD.Respiratory research · 2025Article
- Decoding Hepatocellular Carcinoma Metastasis: Molecular Mechanisms, Targeted Therapies, and Potential Biomarkers.Current issues in molecular biology · 2025Review
- High Mobility Group Box 1 Is Potential Target Therapy for Inhibiting Metastasis and Enhancing Drug Sensitivity of Hepatocellular Carcinoma.International journal of molecular sciences · 2025Article
- Cytoplasmic HuR Expression Enhances Chemoresistance in Pleural Mesothelioma Through Increased Expression of CALB2, Promotion of the E2F Pathway, and Suppression of the p53 Pathway.Thoracic cancer · 2025Article
- Role of Protein Regulators of Cholesterol Homeostasis in Immune Modulation and Cancer Pathophysiology.Endocrinology · 2025Review
- PPP1R12B inhibits cell proliferation by inducing G0/G1 phase arrest via PAK2/β-catenin axis in hepatocellular carcinoma.Frontiers in cell and developmental biology · 2025Article
- The role of ATP-binding cassette subfamily G member 1 in tumor progression.Cancer medicine · 2024Review
- Cuproptosis-related molecular classification and gene signature of hepatocellular carcinoma and experimental verification.Translational cancer research · 2024Article
- Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances.Frontiers in immunology · 2024Review
- Lipid Metabolism as a Potential Target of Liver Cancer.Journal of hepatocellular carcinoma · 2024Review
- Advances in hepatocellular carcinoma drug resistance models.Frontiers in medicine · 2024Review
- Dysregulated cholesterol regulatory genes in hepatocellular carcinoma.European journal of medical research · 2023Review
- P53‑microRNA interactions regulate the response of colorectal tumor cells to oxaliplatin under normoxic and hypoxic conditions.Oncology reports · 2023Article
- β-Lapachone Exerts Anticancer Effects by Downregulating p53, Lys-Acetylated Proteins, TrkA, p38 MAPK, SOD1, Caspase-2, CD44 and NPM in Oxaliplatin-Resistant HCT116 Colorectal Cancer Cells.International journal of molecular sciences · 2023Article
- SAM-Competitive EZH2-Inhibitors Induce Platinum Resistance by EZH2-Independent Induction of ABC-Transporters.Cancers · 2023Article
- β-Catenin signaling in hepatocellular carcinoma.The Journal of clinical investigation · 2022Review
- Silenced LINC01134 Enhances Oxaliplatin Sensitivity by Facilitating Ferroptosis Through GPX4 in Hepatocarcinoma.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
backgroundChemo-resistance in hepatocellular carcinoma (HCC) is a major problem, and acquired drug resistance prevents cancer therapies from achieving complete responses. Molecular targeting therapy presents an opportunity to impede tumor through combination or sequential therapy, while the accurate effect is vague.
methodsThe efficacy of combinations between oxaliplatin and anti-cancer molecular targeting drugs was screened. Strangely, the combined chemotherapy with oxaliplatin and saracatinib induced significantly antagonistic effects. Then the antitumor effects of combined treatment with saracatinib and oxaliplatin were confirmed in wide type HCC as well as in saracatinib- and oxaliplatin-resistant HCC. RNA sequencing was used to explore the resistance mechanism, and the roles of ATP-binding cassette transporter G1 (ABCG1) and Wnt signaling in oxaliplatin resistance were confirmed.
resultsChemotherapy with oxaliplatin and saracatinib individually induced strong anti-HCC effects, while combined or sequential treatment of HCC cells with these two drugs exhibited reduced efficacy compared to treatment with the single drugs. And it was saracatinib treatment caused oxaliplatin resistance. RNA sequencing revealed 458 genes that were altered by treatment with saracatinib and oxaliplatin. Of these, the gene encoding ABCG1 and Wnt-associated genes were significantly upregulated. Upregulation of ABCG1 and oxaliplatin resistance were associated with activation of Wnt signaling. Interference with ABCG1 expression or inhibition of Wnt signaling resulted in reversal of the saracatinib-induced oxaliplatin resistance in HCC.
conclusionsThese studies demonstrated that combined or sequential chemotherapy with oxaliplatin and saracatinib reduced antitumor efficacy, and this antagonism was attributed to the activation of Wnt signaling and upregulation of ABCG1 by saracatinib.
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