ArticlePharmaceuticals (Basel, Switzerland)2022
Berberine Overcomes Gemcitabine-Associated Chemoresistance through Regulation of Rap1/PI3K-Akt Signaling in Pancreatic Ductal Adenocarcinoma.
Article in Pharmaceuticals (Basel, Switzerland), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Phytochemicals as Multitarget Therapeutics in Pancreatic Cancer: Mechanisms, Clinical Evidence, and Translational Challenges.Phytotherapy research : PTR · 2026Review
- Article
- Cellular and Molecular Mechanisms of Berberine in Cancer Therapy: Recent Advances.Archiv der Pharmazie · 2026Review
- Berberine as a Multifunctional Adjuvant in Cancer Therapy: Mechanistic Insights, Nanotechnological Strategies, and Translational Challenges.Pharmaceuticals (Basel, Switzerland) · 2026Review
- Research progress of plant-derived chemical compounds for overcoming pancreatic cancer drug resistance.World journal of gastroenterology · 2026Review
- Saikosaponin D overcomes gemcitabine resistance in pancreatic cancer via AKT/mTOR pathway inhibition and synergistic induction of apoptosis and autophagy.Oncology reports · 2026Article
- [Overexpression of lncRNA SNHG12 promotes docetaxel resistance of prostate cancer cells by activating PI3K/AKT signalingNan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Ras-proximate-1 (RAP1): a prognosis and therapeutic target in the metastatic spread of breast cancer.Clinical & experimental metastasis · 2025Review
- Synergistic Anti-Cancer Activities of Curcumin Derivative CU17 Combined with Gemcitabine Against A549 Non-Small-Cell Lung Cancer Cells.Pharmaceutics · 2025Article
- Targeting the Hippo and Rap1 signaling pathways: the anti-proliferative effects of curcumin in colorectal cancer cell lines.Medical oncology (Northwood, London, England) · 2025Article
- Cancer patient-derived organoids: Novel models for the study of natural products.International journal of biological sciences · 2025Review
- Regulation of the tumor microenvironment by Traditional Chinese Medicine: current progress and future perspectives in oncology.American journal of translational research · 2025Review
- Mechanisms of Berberine in anti-pancreatic ductal adenocarcinoma revealed by integrated multi-omics profiling.Scientific reports · 2024Article
- The LAMB3-EGFR signaling pathway mediates synergistic Anti-Cancer effects of berberine and emodin in Pancreatic cancer.Biochemical pharmacology · 2024Article
- Cholesterol neutralized vemurafenib treatment by promoting melanoma stem-like cells via its metabolite 27-hydroxycholesterol.Cellular and molecular life sciences : CMLS · 2024Article
- Predict lncRNA-drug associations based on graph neural network.Frontiers in genetics · 2024Article
- Integrating Chinese medicine into mainstream cancer therapies: a promising future.Frontiers in oncology · 2024Review
- m6A eraser FTO impairs gemcitabine resistance in pancreatic cancer through influencing NEDD4 mRNA stability by regulating the PTEN/PI3K/AKT pathway.Journal of experimental & clinical cancer research : CR · 2023Article
- Curcumin-Mediated Resistance to Lenvatinib via EGFR Signaling Pathway in Hepatocellular Carcinoma.Cells · 2023Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Gemcitabine (Gem)-based chemotherapy is one of the first-line treatments for pancreatic ductal adenocarcinoma (PDAC). However, its clinical effect is limited due to development of chemoresistance. Various naturally occurring compounds, including Berberine (BBR), provide an anti-cancer efficacy with time-tested safety, individually and in combination with chemotherapeutic drugs. Accordingly, we hypothesized that BBR might enhance the chemosensitivity to Gem in PDAC. In this study, cell culture studies using MIA PaCa-2 and BxPC-3 cells, followed by analysis in patient-derived organoids were performed to evaluate the anti-cancer effects of BBR in PDAC. Considering that cancer is a significant manifestation of increased chronic inflammatory stress, systems biology approaches are prudent for the identification of molecular pathways and networks responsible for phytochemical-induced anti-cancer activity, we used these approaches for BBR-mediated chemosensitization to Gem. Firstly, Gem-resistant (Gem-R) PDAC cells were established, and the combination of BBR and Gem revealed superior anti-cancer efficacy in Gem-R cells. Furthermore, the combination treatment induced cell cycle arrest and apoptosis in Gem-R PDAC cells. Transcriptomic profiling investigated the Rap1 and PI3K-Akt signaling pathway as a key regulator of Gem-resistance and was a key mediator for BBR-mediated chemosensitization in PDAC cells. All cell culture-based findings were successfully validated in patient-derived organoids. In conclusion, we demonstrate that BBR-mediated reversal of chemoresistance to Gem manifests through Rap1/PI3K-Akt signaling in PDAC.
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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.