ArticleOncology research2018
Nelfinavir and Ritonavir Kill Bladder Cancer Cells Synergistically by Inducing Endoplasmic Reticulum Stress.
Article in Oncology research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- Pharmacokinetics of Increased Nelfinavir Plasma Concentrations in Women During Pregnancy and Postpartum.Journal of clinical pharmacology · 2019Trial
- Review
- Rational Identification of Ritonavir as IL-20 Receptor A Ligand Endowed with Antiproliferative Properties in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Construction of a Novel Necroptosis-Related Signature in Rat DRG for Neuropathic Pain.Journal of inflammation research · 2025Article
- Exploring the dual role of endoplasmic reticulum stress in urological cancers: Implications for tumor progression and cell death interactions.Journal of cell communication and signaling · 2024Review
- Ritonavir's Evolving Role: A Journey from Antiretroviral Therapy to Broader Medical Applications.Current oncology (Toronto, Ont.) · 2024Review
- Immunologic Crosstalk of Endoplasmic Reticulum Stress Signaling in Bladder Cancer.Current cancer drug targets · 2024Review
- Salubrinal Enhances Cancer Cell Death during Glucose Deprivation through the Upregulation of xCT and Mitochondrial Oxidative Stress.Biomedicines · 2021Article
- Targeting of FK506 binding protein 5 by miR-203 affects the progression of breast cancer via regulating the fatty acid degradation pathway and potential drug-repurposing.Oncology letters · 2021Article
- Endoplasmic Reticulum Stress and Tumor Microenvironment in Bladder Cancer: The Missing Link.Frontiers in cell and developmental biology · 2021Review
- Drug rechanneling: A novel paradigm for cancer treatment.Seminars in cancer biology · 2021Review
- An Unfolded Protein Response Related Signature Could Robustly Predict Survival Outcomes and Closely Correlate With Response to Immunotherapy and Chemotherapy in Bladder Cancer.Frontiers in molecular biosciences · 2021Article
- Review
- The Anti-Angiogenic Effects of Anti-Human Immunodeficiency Virus Drugs.Frontiers in oncology · 2020Review
- Fluvastatin potentiates anticancer activity of vorinostat in renal cancer cells.Cancer science · 2020Article
- Article
- Interplay between P-Glycoprotein Expression and Resistance to Endoplasmic Reticulum Stressors.Molecules (Basel, Switzerland) · 2018Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human immunodeficiency virus (HIV) protease inhibitor nelfinavir acts against malignancies by inducing endoplasmic reticulum (ER) stress. The HIV protease inhibitor ritonavir, on the other hand, not only induces ER stress but also inhibits P-glycoprotein's pump activity and thereby enhances the effects of its substrate drugs. We therefore postulated that ritonavir in combination with nelfinavir would kill bladder cancer cells effectively by inducing ER stress cooperatively and also enhancing nelfinavir's effect. Nelfinavir was shown to be a P-glycoprotein substrate, and the combination of nelfinavir and ritonavir inhibited bladder cancer cell growth synergistically. It also suppressed colony formation significantly. The combination significantly increased the number of cells in the sub-G1 fraction and also the number of annexin V+ cells, confirming robust apoptosis induction. The combination induced ER stress synergistically, as evidenced by the increased expression of glucose-regulated protein 78, ER-resident protein 44, and endoplasmic oxidoreductin-1-like protein. It also increased the expression of the mammalian target of rapamycin (mTOR) inhibitor AMP-activated protein kinase and caused dephosphorylation of S6 ribosomal protein, demonstrating that the combination also inhibited the mTOR pathway. We also found that the combination enhanced histone acetylation synergistically by decreasing the expression of HDACs 1, 3, and 6.
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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.