ArticleActa pharmacologica Sinica2021
Inhibition of histamine receptor H3 suppresses the growth and metastasis of human non-small cell lung cancer cells via inhibiting PI3K/Akt/mTOR and MEK/ERK signaling pathways and blocking EMT.
Article in Acta pharmacologica Sinica, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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27 citing papers in PubMed, 44 citations in OpenAlex.
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- Targeting histamine signaling: repurposing antihistamines for cancer chemotherapy and immunotherapy.Archives of pharmacal research · 2026Review
- Targeting the nervous system: Mechanistic insights into neuro-tumor communication and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Neural regulation in lung cancer: from mechanisms to new therapeutic perspectives.Clinical and experimental medicine · 2026Review
- LINC00886 inhibits the proliferation, migration, and invasion of NSCLC cells by sponging miR-141-5p.Discover oncology · 2026Article
- RPARP-AS1 Targets miR-10b-5p to Influence Prognosis in Non-Small Cell Lung Cancer and Inhibit Tumor Progression.Analytical cellular pathology (Amsterdam) · 2026Article
- Neurotransmitters and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and Potential Therapeutic Targets.MedComm · 2025Review
- G-protein coupled receptor 183 (GPR183) inhibits visceral metastasis of non-small cell lung cancer.Clinical & experimental metastasis · 2025Article
- Histamine HInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- ESPN activates ZEB1-mediated EMT through the PI3K/AKT/mTOR axis to promote osteosarcoma metastasis.Journal of translational medicine · 2025Article
- Cinobufagin Enhances the Sensitivity of Cisplatin-Resistant Lung Cancer Cells to Chemotherapy by Inhibiting the PI3K/AKT and MAPK/ERK Pathways.Journal of cellular and molecular medicine · 2025Article
- The Use of Biologics for Targeting GPCRs in Metastatic Cancers.Biotech (Basel (Switzerland)) · 2025Review
- ITGB4 is a prognostic biomarker and correlated with lung adenocarcinoma brain metastasis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- Mechanisms of Bone Morphogenetic Protein 2 in Respiratory Diseases.Current allergy and asthma reports · 2024Review
- Pathophysiological role of histamine signaling and its implications in glioblastoma.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- AR71, Histamine HInternational journal of molecular sciences · 2024Article
- PI3K/AKT pathway as a pivotal regulator of epithelial-mesenchymal transition in lung tumor cells.Cancer cell international · 2024Review
- Magnolol and 5-fluorouracil synergy inhibition of metastasis of cervical cancer cells by targeting PI3K/AKT/mTOR and EMT pathways.Chinese herbal medicines · 2024Article
- Selenium-binding protein 1 inhibits malignant progression and induces apoptosis via distinct mechanisms in non-small cell lung cancer.Cancer medicine · 2023Article
- Expression pattern and prognostic potential of histamine receptors in epithelial ovarian cancer.Journal of cancer research and clinical oncology · 2023Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent evidence shows that the expression levels of histamine receptor H3 (Hrh3) are upregulated in several types of cancer. However, the role of Hrh3 in non-small cell lung cancer (NSCLC) has not been elucidated. In the present study, we showed that the expression levels of Hrh3 were significantly increased in NSCLC samples, and high levels of Hrh3 were associated with poor overall survival (OS) in NSCLC patients. In five human NSCLC cell lines tested, Hrh3 was significantly upregulated. In NSCLC cell lines H1975, H460, and A549, Hrh3 antagonist ciproxifan (CPX, 10-80 μM) exerted moderate and concentration-dependent inhibition on the cell growth and induced apoptosis, whereas its agonist RAMH (80 μM) reversed these effects. Furthermore, inhibition of Hrh3 by CPX or siRNA retarded the migration and invasion of NSCLC cells through inhibiting epithelial-mesenchymal transition (EMT) progression via reducing the phosphorylation of PI3K/Akt/mTOR and MEK/ERK signaling pathways. In nude mice bearing H1975 cell xenograft or A549 cell xenograft, administration of CPX (3 mg/kg every other day, intraperitoneal) significantly inhibited the tumor growth with increased E-cadherin and ZO-1 expression and decreased Fibronectin expression in tumor tissue. In conclusion, this study reveals that Hrh3 plays an important role in the growth and metastasis of NSCLC; it might be a potential therapeutic target against the lung cancer.
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