ArticleEXCLI journal2021
Angiotensin receptor blocker Losartan inhibits tumor growth of colorectal cancer.
Article in EXCLI journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 33 citations in OpenAlex.
- Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances.International journal of molecular sciences · 2026Review
- Review
- Current Status of Research on Losartan in Tumour Therapy.Journal of cellular and molecular medicine · 2026Review
- Angiotensin receptor-neprilysin inhibitors improve the outcome of lung cancer patients with hypertension undergoing immune checkpoint inhibitors treatment.BMC cardiovascular disorders · 2025Article
- Innovative horizons: harnessing drug repositioning for targeted therapeutics in colorectal cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- Aging and the extracellular matrix: A tumor-permissive microenvironment driving cancer progression.Current opinion in biomedical engineering · 2025Article
- Monod: model-based discovery and integration through fitting stochastic transcriptional dynamics to single-cell sequencing data.Nature methods · 2025Article
- The Road to Precision Nanomedicine: An Insight on Drug Repurposing and Advances in Nanoformulations for Treatment of Cancer.AAPS PharmSciTech · 2025Review
- Exploring the Mechanism of Canmei Formula in Preventing and Treating Recurrence of Colorectal Adenoma Based on Data Mining and Algorithm Prediction.Biological procedures online · 2025Article
- Rethinking corticosteroids use in oncology.Frontiers in pharmacology · 2025Article
- The synergistic potential of mechanotherapy and sonopermeation to enhance cancer treatment effectiveness.npj biological physics and mechanics · 2025Review
- Exploring Immune Cell Infiltration and Small Molecule Compounds for Ulcerative Colitis Treatment.Genes · 2024Article
- Drug Repurposing for Cancer Treatment: A Comprehensive Review.International journal of molecular sciences · 2024Review
- Review
- Angiotensin receptor blocker attacks armored and cold tumors and boosts immune checkpoint blockade.Journal for immunotherapy of cancer · 2024Article
- Modulation of ACE2/Ang1-7/Mas and ACE/AngII/AT1 axes affects anticancer properties of sertraline in MCF-7 breast cancer cells.Biochemistry and biophysics reports · 2024Article
- One Molecule, Many Faces: Repositioning Cardiovascular Agents for Advanced Wound Healing.Molecules (Basel, Switzerland) · 2024Review
- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
- Several first-line anti-hypertensives act on fibrosarcoma progression and PD1ab blockade therapy.Journal of orthopaedic surgery and research · 2024Article
- Losartan as a Reproposing Therapeutic Agent in Acute Respiratory Distress Syndrome: Modulating Inflammatory Responses and Cytokine Production.International journal of molecular and cellular medicine · 2024Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The renin-angiotensin system (RAS) is up-regulated in patients with colorectal cancer (CRC) and is reported to be associated with poor prognosis and chemo-resistance. Here we explored the therapeutic potential of targeting RAS in CRC using Losartan, an angiotensin receptor blocker. An integrative-systems biology approach was used to explore a proteome-level dataset of a gene signature that is modulated by Losartan. The anti-proliferative activity of Losartan was evaluated using 2- and 3-dimensional cell culture models. A xenograft model of colon cancer was used to investigate tumor growth with Losartan alone and in combination with 5-FU followed by histological staining (Hematoxylin & Eosin and Masson trichrome staining), biochemical analyses, gene expression analyses by RT-PCR, western blot/IHC, or MMP Gelatin Zymography studies. Effects on cell cycle and cell death were assessed by flow cytometry. Losartan inhibited cell growth and suppressed cell cycle progression, causing an increase in CRC cells in the G1 phase. Losartan significantly reduced tumor growth and enhanced tumor cell necrosis. An impact on the inflammatory response, including up-regulation of pro-inflammatory cytokines and chemokines in CRC cells are potential mechanisms that could partially explain Losartan's anti-proliferative effects. Moreover, metastasis and angiogenesis were reduced in Losartan-treated mice as observed by inhibited matrix metalloproteinase-2 and -9 activities and decreased tumor vasculature. These data demonstrate the therapeutic potential of combining chemotherapeutic regimens with Losartan to synergistically enhance its activity and target the renin-angiotensin system as a new approach in colorectal cancer treatment.
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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.