ArticleOncotarget2015
Proton pump inhibitors enhance the effects of cytotoxic agents in chemoresistant epithelial ovarian carcinoma.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04874935 (The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer), which is not on this map. Cited by 26 papers.
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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.
The Possible Efficacy and Safety of Lansoprazole Co-administration With Neoadjuvant Chemotherapy in Women With Breast Cancer
Who cites it
26 citing papers in PubMed, 56 citations in OpenAlex.
- ATP6V1B1 regulates ovarian cancer progression and cisplatin sensitivity through the mTOR/autophagy pathway.Molecular and cellular biochemistry · 2025Article
- Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner.Open life sciences · 2024Article
- Proton pump inhibitors display anti-tumour potential in glioma.Cell proliferation · 2023Review
- Esomeprazole Alleviates Cisplatin Resistance by Inhibiting the AKT/mTOR Pathway in Ovarian Cancer Cells.OncoTargets and therapy · 2023Article
- Article
- The V-ATPases in cancer and cell death.Cancer gene therapy · 2022Review
- Proposal to Consider Chemical/Physical Microenvironment as a New Therapeutic Off-Target Approach.Pharmaceutics · 2022Article
- Proton Pump Inhibitors Enhance the Antitumor Effect of Chemotherapy for Esophageal Squamous Cell Carcinoma.Cancers · 2022Article
- Proton pump inhibitors and sensitization of cancer cells to radiation therapy.Frontiers in oncology · 2022Review
- Patient-derived tumor models are attractive tools to repurpose drugs for ovarian cancer treatment: pre-clinical updates.Oncotarget · 2022Review
- Targeting the Interplay between Cancer Metabolic Reprogramming and Cell Death Pathways as a Viable Therapeutic Path.Biomedicines · 2021Review
- Therapeutic prevention of COVID-19 in elderly: a case-control study.GeroScience · 2021Article
- A Quantitative Pharmacology Model of Exosome-Mediated Drug Efflux and Perturbation-Induced Synergy.Pharmaceutics · 2021Article
- The role of hypoxia in the tumor microenvironment and development of cancer stem cell: a novel approach to developing treatment.Cancer cell international · 2021Review
- Widely available lysosome targeting agents should be considered as potential therapy for COVID-19.International journal of antimicrobial agents · 2020Article
- A New and Integral Approach to the Etiopathogenesis and Treatment of Breast Cancer Based upon Its Hydrogen Ion Dynamics.International journal of molecular sciences · 2020Review
- Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.Oxidative medicine and cellular longevity · 2020Review
- Proton pump inhibitors can reverse the YAP mediated paclitaxel resistance in epithelial ovarian cancer.BMC molecular and cell biology · 2019Article
- Role of hypoxia in cancer therapy by regulating the tumor microenvironment.Molecular cancer · 2019Review
- Overcoming transporter-mediated multidrug resistance in cancer: failures and achievements of the last decades.Drug delivery and translational research · 2019Review
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
This study was designed to investigate whether proton pump inhibitors (PPI, V-ATPase blocker) could increase the effect of cytotoxic agents in chemoresistant epithelial ovarian cancer (EOC). Expression of V-ATPase protein was evaluated in patients with EOC using immunohistochemistry, and patient survival was compared based on expression of V-ATPase mRNA from a TCGA data set. In vitro, EOC cell lines were treated with chemotherapeutic agents with or without V-ATPase siRNA or PPI (omeprazole) pretreatment. Cell survival and apoptosis was assessed using MTT assay and ELISA, respectively. In vivo experiments were performed to confirm the synergistic effect with omeprazole and paclitaxel on tumor growth in orthotopic and patient-derived xenograft (PDX) mouse models. Expression of V-ATPase protein in ovarian cancer tissues was observed in 44 patients (44/59, 74.6%). Higher expression of V-ATPase mRNA was associated with poorer overall survival in TCGA data. Inhibition of V-ATPase by siRNA or omeprazole significantly increased cytotoxicity or apoptosis to paclitaxel in chemoresistant (HeyA8-MDR, SKOV3-TR) and clear cell carcinoma cells (ES-2, RMG-1), but not in chemosensitive cells (HeyA8, SKOV3ip1). Moreover, the combination of omeprazole and paclitaxel significantly decreased the total tumor weight compared with paclitaxel alone in a chemoresistant EOC animal model and a PDX model of clear cell carcinoma. However, this finding was not observed in chemosensitive EOC animal models. These results show that omeprazole pretreatment can increase the effect of chemotherapeutic agents in chemoresistant EOC and clear cell carcinoma via reduction of the acidic tumor microenvironment.
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