ArticleCell & bioscience2019
Combination chemotherapy of valproic acid (VPA) and gemcitabine regulates STAT3/Bmi1 pathway to differentially potentiate the motility of pancreatic cancer cells.
Article in Cell & bioscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 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
23 citing papers in PubMed, 58 citations in OpenAlex.
- Valproic acid sensitizes resveratrol to induce glioma cell apoptosis via the ROS-PDCD4-Bax signaling axis.Frontiers in cell and developmental biology · 2026Article
- Valproic Acid as a Histone Deacetylase Inhibitor InducesCurrent issues in molecular biology · 2025Article
- Valproic Acid Reduces Invasiveness and Cellular Growth in 2D and 3D Glioblastoma Cell Lines.International journal of molecular sciences · 2025Article
- A New Treatment Strategy for Lung Cancer With HDAC and Wnt/β-Catenin Pathway Inhibitors.IUBMB life · 2025Article
- Repurposing Antiepileptic Drugs for Cancer: A Promising Therapeutic Strategy.Journal of clinical medicine · 2025Review
- Article
- Gemcitabine Modulates HLA-I Regulation to Improve Tumor Antigen Presentation by Pancreatic Cancer Cells.International journal of molecular sciences · 2024Article
- Correction: Combination chemotherapy of valproic acid (VPA) and gemcitabine regulates STAT3/Bmi1 pathway to differentially potentiate the motility of pancreatic cancer cells.Cell & bioscience · 2023Article
- High glucose-upregulated PD-L1 expression through RAS signaling-driven downregulation of PTRH1 leads to suppression of T cell cytotoxic function in tumor environment.Journal of translational medicine · 2023Article
- A comprehensive review on pharmacological applications and drug-induced toxicity of valproic acid.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Synergistic combination of doxorubicin with hydralazine, and disulfiram against MCF-7 breast cancer cell line.PloS one · 2023Article
- Targeting pancreatic cancer immune evasion by inhibiting histone deacetylases.World journal of gastroenterology · 2022Review
- The Class I HDAC Inhibitor Valproic Acid Strongly Potentiates Gemcitabine Efficacy in Pancreatic Cancer by Immune System Activation.Biomedicines · 2022Article
- Hyperglycemia Enhances Immunosuppression and Aerobic Glycolysis of Pancreatic Cancer Through Upregulating Bmi1-UPF1-HK2 Pathway.Cellular and molecular gastroenterology and hepatology · 2022Article
- Valproic Acid Sensitizes Glioma Cells to Luteolin Through Induction of Apoptosis and Autophagy via Akt Signaling.Cellular and molecular neurobiology · 2021Article
- Article
- Reactive Oxygen Species-Mediated Mitochondrial Dysfunction Triggers Sodium Valproate-Induced Cytotoxicity in Human Colorectal Adenocarcinoma Cells.Journal of gastrointestinal cancer · 2021Article
- Combined evaluation of proliferation and apoptosis to calculate ICMedical oncology (Northwood, London, England) · 2021Article
- Chemotherapeutic drugs: Cell death- and resistance-related signaling pathways. Are they really as smart as the tumor cells?Translational oncology · 2021Review
- Sodium Valproate, a Histone Deacetylase Inhibitor, Provokes Reactive Oxygen Species-Mediated Cytotoxicity in Human Hepatocellular Carcinoma Cells.Journal of gastrointestinal cancer · 2021Article
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGemcitabine is the standard first-line chemotherapy regimen for pancreatic cancer. However, its therapeutic value is substantially limited in pancreatic cancer patients due to occurrence of resistance towards gemcitabine. A strategy of combined chemo-regimens is widely employed in clinical settings in attempt to reduce the chance of developing therapeutic resistance. Valproic acid (VPA) has been reported as a promising anticancer drug in various clinical trials and studies. However, the clinical value and potential dose-effect of VPA in combination with gemcitabine for pancreatic cancer treatment are under investigated.
resultsIn this study, we determined the synergistic effect of VPA and gemcitabine and found that high-dose VPA significantly and dose-dependently enhanced the sensitivity of pancreatic cancer cells to gemcitabine. Intriguingly, low-dose VPA potentiated the migration and invasion of pancreatic cancer cells that already showed gemcitabine-induced motility. Moreover, low-dose VPA increased the reactive oxygen species (ROS) production, which activated AKT to further stimulate the activation of STAT3, Bmi1 expression and eventually promoted the migration and invasion of pancreatic cancer cells induced by gemcitabine. Whereas high-dose VPA stimulated excessive ROS accumulation that promoted p38 activation, which suppressed the activation of STAT3 and Bmi1.
conclusionPancreatic cancer cells respond differentially towards low- or high-dose of VPA in combination with gemcitabine, and a low VPA further potentiate pancreatic cancer cell to migrate and invade. Our results suggest that STAT3/Bmi1 signaling cascade, which is regulated by ROS-dependent, AKT- or p38-modulated pathways, primarily mediated the sensitivity and motility of pancreatic cancer cells towards combined gemcitabine and VPA regimen. These findings suggest a highly clinically relevant new mechanism of developing resistance against combined chemo-regimens, warranting further mechanistic and translational exploration for VPA in combination with gemcitabine and other chemotherapies.
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.