ArticleMolecular pharmaceutics2017
Cetuximab Prevents Methotrexate-Induced Cytotoxicity in Vitro through Epidermal Growth Factor Dependent Regulation of Renal Drug Transporters.
Article in Molecular pharmaceutics, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05105009 (Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function), which is not on this map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Furosemide and Creatinine Tubular Stress Test in Order to Measure Proximal Tubule Residual Function: is It Better Than GFR?
Who cites it
14 citing papers in PubMed, 34 citations in OpenAlex.
- Transition to fetal calf serum-free culture enhances kidney proximal tubule cell bioenergetics and allows pharmacological applications.Cell and tissue research · 2026Article
- Amino acids protect against methotrexate-induced hepatorenal toxicity in vitro and in vivo.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Estimation of Proximal Tubular Function by Stimulation of Organic Anion and Cation Transporters.Journal of the American Society of Nephrology : JASN · 2025Article
- Renal Organic Anion Transporters 1 and 3 In Vitro: Gone but Not Forgotten.International journal of molecular sciences · 2023Review
- Recapitulating the Pharmacological Interactions of Cetuximab with Sunitinib and Cisplatin in Head and Neck Carcinoma Cells in vitro.Pharmacology · 2023Article
- In Vitro Characterization of Renal Drug Transporter Activity in Kidney Cancer.International journal of molecular sciences · 2022Article
- Review
- Review
- Nephrotoxic antisense oligonucleotide SPC5001 induces kidney injury biomarkers in a proximal tubule-on-a-chip.Archives of toxicology · 2021Article
- HPV-associated penile cancer: Impact of copy number alterations in miRNA/mRNA interactions and potential druggable targets.Cancer biomarkers : section A of Disease markers · 2021Observational
- Multidrug transporter MRP4/ABCC4 as a key determinant of pancreatic cancer aggressiveness.Scientific reports · 2020Article
- Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Screening of Drug-Transporter Interactions in a 3D Microfluidic Renal Proximal Tubule on a Chip.The AAPS journal · 2018Article
- Beyond Competitive Inhibition: Regulation of ABC Transporters by Kinases and Protein-Protein Interactions as Potential Mechanisms of Drug-Drug Interactions.Drug metabolism and disposition: the biological fate of chemicals · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The combination of methotrexate with epidermal growth factor receptor (EGFR) recombinant antibody, cetuximab, is currently being investigated in treatment of head and neck carcinoma. As methotrexate is cleared by renal excretion, we studied the effect of cetuximab on renal methotrexate handling. We used human conditionally immortalized proximal tubule epithelial cells overexpressing either organic anion transporter 1 or 3 (ciPTEC-OAT1/ciPTEC-OAT3) to examine OAT1 and OAT3, and the efflux pumps breast cancer resistance protein (BCRP), multidrug resistance protein 4 (MRP4), and P-glycoprotein (P-gp) in methotrexate handling upon EGF or cetuximab treatment. Protein kinase microarrays and knowledge-based pathway analysis were used to predict EGFR-mediated transporter regulation. Cytotoxic effects of methotrexate were evaluated using the dimethylthiazol bromide (MTT) viability assay. Methotrexate inhibited OAT-mediated fluorescein uptake and decreased efflux of Hoechst33342 and glutathione-methylfluorescein (GS-MF), which suggested involvement of OAT1/3, BCRP, and MRP4 in transepithelial transport, respectively. Cetuximab reversed the EGF-increased expression of OAT1 and BCRP as well as their membrane expressions and transport activities, while MRP4 and P-gp were increased. Pathway analysis predicted cetuximab-induced modulation of PKC and PI3K pathways downstream EGFR/ERBB2/PLCg. Pharmacological inhibition of ERK decreased expression of OAT1 and BCRP, while P-gp and MRP4 were increased. AKT inhibition reduced all transporters. Exposure to methotrexate for 24 h led to a decreased viability, an effect that was reversed by cetuximab. In conclusion, cetuximab downregulates OAT1 and BCRP while upregulating P-gp and MRP4 through an EGFR-mediated regulation of PI3K-AKT and MAPKK-ERK pathways. Consequently, cetuximab attenuates methotrexate-induced cytotoxicity, which opens possibilities for further research into nephroprotective comedication therapies.
Indexed as
Identifiers
What 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.