ArticleOncology letters2025
Bortezomib overcomes TRAIL resistance in Burkitt's lymphoma by enhancing apoptosis via reactive oxygen species-mediated DR5 upregulation and MAPK pathway activation.
Article in Oncology letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
2 citing papers in PubMed.
- Helping Apo2L/TRAIL in the Battle: Synergistic Therapeutic Approaches for Cancer Therapies.International journal of molecular sciences · 2026Review
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills tumor cells and exerts minimal toxic effects on normal cells. However, resistance to TRAIL-induced apoptosis is a major obstacle in the clinical application of TRAIL. Bortezomib can enhance the tumor-killing effect of TRAIL in certain tumors, but understanding in Burkitt's lymphoma (BL), especially in TRAIL-resistant BL cells, is limited. Therefore, the present study aimed to assess the synergistic effect of bortezomib and TRAIL in BL. Using the Raji cell line, the least susceptible to TRAIL among BL cell lines, the present study assessed the effect and mechanism by which bortezomib reverses resistance to TRAIL. Cell proliferation inhibition was assessed using the Cell Counting Kit-8 assay. Apoptosis was assessed by flow cytometry. Intracellular reactive oxygen species (ROS) were detected with DCFH-DA, and mitochondrial membrane potential was measured using JC-1. Expression levels of apoptosis proteins and MAPK signaling pathway-related proteins were analyzed by western blot. Combination of bortezomib and TRAIL strongly and synergistically inhibited Raji and CA46 BL cell proliferation. Furthermore, the combination of bortezomib and TRAIL was associated with the following: Induction of apoptosis; increased levels of ROS; presence of mitochondrial membrane potential disorders; upregulation of the levels of apoptosis-related proteins cleaved caspase 8/9/3 and cleaved poly (ADP-ribose) polymerase; and downregulation of the levels of antiapoptotic factors Bcl-2 and Bcl-xl. In addition, bortezomib induced a significant increase in the expression levels of death receptor 5 (DR5), a TRAIL receptor. Pretreatment with the antioxidant N-acetylcysteine inhibited not only ROS upregulation but also DR5 upregulation induced by bortezomib in Raji cells. Furthermore, the present study revealed that the combination of bortezomib and TRAIL could regulate the levels of MAPK signaling pathway-related proteins, such as phosphorylated extracellular signal-regulated kinase 1/2, phosphorylated (p-)p38, p-c-Jun, p-activating transcription factor 2 and phosphorylated stress-activated protein kinase/c-Jun N-terminal kinase. Therefore, the results indicate that bortezomib may enhance Raji cell sensitivity to TRAIL via ROS-dependent upregulation of DR5, induce apoptosis through the MAPK signaling pathway, and subsequently inhibit cell proliferation. Additionally, bortezomib combined with TRAIL had a potential synergistic apoptosis-inducing effect in TRAIL-resistant BL cells.
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.