ArticleDaru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences2026
BAY-876 restores lenvatinib sensitivity in resistant hepatocellular carcinoma cells by disrupting the GLUT1-SLC7A11-NADPH redox axis.
Article in Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAcquired resistance limits the efficacy of lenvatinib in hepatocellular carcinoma (HCC). This study evaluated whether GLUT1 inhibition by BAY-876 reverses lenvatinib resistance by disrupting SLC7A11-associated redox buffering.
methodsLenvatinib-resistant HuH-7-LR and Hep 3B-LR cells were generated by stepwise drug exposure. Drug sensitivity, combination synergy, glucose uptake, colony formation, migration, ATP, NADPH/NADP⁺ and GSH/GSSG ratios, intracellular thiols, ROS, apoptosis, gene and protein expression, N-acetyl-L-cysteine (NAC) rescue, and SLC7A11 knockdown were evaluated.
resultsResistant cells exhibited increased lenvatinib IC₅₀ values, glucose uptake, and GLUT1/SLC7A11 expression. BAY-876 preferentially inhibited glucose uptake and viability in resistant cells and restored lenvatinib sensitivity to near-parental levels. Combined treatment produced synergistic growth inhibition, reduced colony formation and migration, depleted ATP and NADPH, disrupted GSH/GSSG balance, decreased intracellular thiols, and increased ROS. It also induced apoptosis, evidenced by Annexin V positivity, caspase-3/7 activation, BAX induction, BCL2 suppression, and PARP/caspase-3 cleavage. NAC partially restored viability and redox balance. SLC7A11 knockdown reduced BAY-876-associated thiol depletion and ROS accumulation, supporting an SLC7A11-dependent redox component.
conclusionBAY-876 resensitized lenvatinib-resistant HCC cells by restricting glucose uptake, disrupting NADPH-dependent redox buffering, and promoting redox stress-induced apoptosis. These findings support the GLUT1-SLC7A11-NADPH axis as an in vitro therapeutic vulnerability, while definitive evidence of disulfidptosis requires further investigation.
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.