ArticleOncotarget2016
MRP3 as a novel resistance factor for sorafenib in hepatocellular carcinoma.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 66 citations in OpenAlex.
- Alcohol induces sorafenib resistance in hepatocellular carcinoma: A translational study.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Immunotherapy and liver transplantation for hepatocellular carcinoma: Current and future challenges.World journal of transplantation · 2025Review
- Coordinated activation of DNMT3a and TET2 in cancer stem cell-like cells initiates and sustains drug resistance in hepatocellular carcinoma.Cancer cell international · 2024Article
- Mechanisms of Sorafenib Resistance in HCC Culture Relate to the Impaired Membrane Expression of Organic Cation Transporter 1 (OCT1).Journal of hepatocellular carcinoma · 2024Article
- Extracellular Vesicles and Cancer Multidrug Resistance: Undesirable Intercellular Messengers?Life (Basel, Switzerland) · 2023Review
- The critical role of circular RNAs in drug resistance in gastrointestinal cancers.Medical oncology (Northwood, London, England) · 2023Review
- The Roles of Epigenetic Regulation and the Tumor Microenvironment in the Mechanism of Resistance to Systemic Therapy in Hepatocellular Carcinoma.International journal of molecular sciences · 2023Review
- Immunotherapy for hepatocellular carcinoma: A promising therapeutic option for advanced disease.World journal of hepatology · 2022Review
- Expression of Chemoresistance-Associated ABC Proteins in Hepatobiliary, Pancreatic and Gastrointestinal Cancers.Cancers · 2022Review
- Sorafenib Chemosensitization by Caryophyllane Sesquiterpenes in Liver, Biliary, and Pancreatic Cancer Cells: The Role of STAT3/ABC Transporter Axis.Pharmaceutics · 2022Article
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- The implications of ABCC3 in cancer drug resistance: can we use it as a therapeutic target?American journal of cancer research · 2021Review
- Review
- Cancer-associated adipocytes promote pancreatic cancer progression through SAA1 expression.Cancer science · 2020Article
- Potential use of lenvatinib for patients with unresectable hepatocellular carcinoma including after treatment with sorafenib: Real-world evidence andOncotarget · 2020Article
- Review
- Repurposing Tyrosine Kinase Inhibitors to Overcome Multidrug Resistance in Cancer: A Focus on Transporters and Lysosomal Sequestration.International journal of molecular sciences · 2020Review
- Review
- Hypoxia-Induced Aquaporin-3 Changes Hepatocellular Carcinoma Cell Sensitivity to Sorafenib by Activating the PI3K/Akt Signaling Pathway.Cancer management and research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The mechanism of resistance of hepatocellular carcinoma (HCC) to sorafenib is unknown and no useful predictive biomarker for sorafenib treatment has been reported. Accordingly, we established sorafenib-resistant HCC cells and investigated the underlying mechanism of resistance to sorafenib. Sorafenib-resistant cell lines were established from the HCC cell line PLC/PRF5 by cultivation under continuous exposure to increasing concentration of sorafenib. The IC50 values of the 2 resistant clones PLC/PRF5-R1 and PLC-PRF5-R2 were 9.2±0.47 μM (1.8-fold) and 25±5.1 μM (4.6-fold) respectively, which were significantly higher than that of parental PLC/PRF5 cells (5.4±0.17 μM) (p < 0.01 respectively), as determined by MTT assay. Western blot analysis of signal transduction-related proteins showed no significant differences in expression of AKT/pAKT, mTOR/pmTOR, or ERK/pERK between the 2 resistant clones versus parent cells, suggesting no activation of an alternative signal transduction pathway. Likewise, when expression of membrane transporter proteins was determined, there were no significant differences in expression levels of BSEP, MDR1, MRP2, BCRP, MRP4 and OCT1 between resistant clones and parent cells. However, the expression levels of MRP3 in the 2 resistant clones were significantly higher than that of parent cells. When MRP3 gene was knocked down by siRNA in PLC-PRF5-R2 cells, the sensitivity of the cells to sorafenib was restored. In the analysis of gene mutation, there was no mutation in the activation segment of Raf1 kinase in the resistant clones. Our data clearly demonstrate that the efflux transporter MRP3 plays an important role in resistance to sorafenib in HCC cells.
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