ArticleInternational journal of biological sciences2018
Combined inhibition of autophagy and Nrf2 signaling augments bortezomib-induced apoptosis by increasing ROS production and ER stress in pancreatic cancer cells.
Article in International journal of biological sciences, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers, 1 of them a synthesis that pooled it.
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
36 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Dual roles and therapeutic potential of Keap1-Nrf2 pathway in pancreatic cancer: a systematic review.Cell communication and signaling : CCS · 2019Pooled it
- Calcium overload-induced apoptosis in cancer cells: ER-mitochondria crosstalk and therapeutic implications.Pharmaceutical science advances · 2026Review
- Article
- Insights into the Impact of Low-Dose Ionizing Radiation on Neurodegenerative Disease Progression in In Vivo Models.International journal of molecular sciences · 2026Review
- EP4 influences bortezomib resistance in multiple myeloma by modulating endoplasmic reticulum stress via the phosphatidylinositol 3-kinase/protein kinase B pathway.Anti-cancer drugs · 2026Article
- Cyclin C promotes pancreatic developmentand suppresses cancer initiation by maintenance of the autophagy-lysosome pathway.iScience · 2026Article
- Wogonin derivative V8 enhances bortezomib efficacy in gastric carcinoma by disrupting lysosome-mediated drug resistance.World journal of gastroenterology · 2026Article
- Decoding NF-κB: nucleocytoplasmic shuttling dynamics, synthetic modulation and post-therapeutic behavior in cancer.Molecular biology reports · 2025Review
- Ubiquitination regulates autophagy in cancer: simple modifications, promising targets.Journal of translational medicine · 2024Review
- NRF2 Suppression Enhances the Susceptibility of Pancreatic Cancer Cells, Miapaca-2 to Paclitaxel.Molecular biotechnology · 2024Article
- TRIM44, a Novel Prognostic Marker, Supports the Survival of Proteasome-Resistant Multiple Myeloma Cells.Cells · 2024Article
- Precision Targeting Strategies in Pancreatic Cancer: The Role of Tumor Microenvironment.Cancers · 2024Review
- ER Stress-Activated HSF1 Governs Cancer Cell Resistance to USP7 Inhibitor-Based Chemotherapy through the PERK Pathway.International journal of molecular sciences · 2024Article
- Nrf2 in human cancers: biological significance and therapeutic potential.American journal of cancer research · 2024Review
- Combination therapy with HSP90 inhibitors and piperlongumine promotes ROS-mediated ER stress in colon cancer cells.Cell death discovery · 2023Article
- TRIM21-Promoted FSP1 Plasma Membrane Translocation Confers Ferroptosis Resistance in Human Cancers.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Molecular Hydrogen: an Emerging Therapeutic Medical Gas for Brain Disorders.Molecular neurobiology · 2023Review
- STOML2 restricts mitophagy and increases chemosensitivity in pancreatic cancer through stabilizing PARL-induced PINK1 degradation.Cell death & disease · 2023Article
- Article
- Emodin Ameliorates the Efficacy of Carfilzomib in Multiple Myeloma Cells via Apoptosis and Autophagy.Biomedicines · 2022Article
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 at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer (PC) is highly resistant to current therapies; thus, there is an urgent need to develop new treatment strategies. The proteasome is crucially important for proteostasis, which is involved in cell proliferation and survival, making it an attractive therapeutic target in cancer. However, recent studies have indicated that bortezomib, a highly selective proteasome inhibitor, has limited effects in solid tumors including PC. Thus, more mechanistic insights into chemo-sensitization strategies for bortezomib are urgently needed. Herein, we demonstrate that bortezomib induced apoptosis and autophagy via a mechanism involving endoplasmic reticulum (ER) stress in PC cells. Additionally, bortezomib treatment led to increased levels of intracellular reactive oxygen species (ROS), which play critical roles in bortezomib-induced ER stress and apoptosis. Moreover, autophagy functions as a compensatory mechanism to eliminate bortezomib-induced ROS and resists ER stress-mediated apoptosis. Additionally, the Nrf2-mediated antioxidative response, which works against with bortezomib-induced autophagy, also protected cells against bortezomib-induced ROS production. Finally, the dual inhibition of autophagy and Nrf2 signaling cooperatively enhanced bortezomib-induced apoptosis by elevating ROS levels and ER stress. Together, these data demonstrate that activation of autophagy and the Nrf2 antioxidant system, which lowers intracellular ROS, are mechanistically how PC cells overcome bortezomib treatment. In summary, combining proteasome inhibitors with drugs targeting autophagy and Nrf2 signaling could be a promising therapeutic approach for PC treatment.
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.