ArticlePharmaceutical research2023
TGF-β Signaling Activation Confers Anlotinib Resistance in Gastric Cancer.
Article in Pharmaceutical research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 4 citations in OpenAlex.
- A three-gene signature correlated with MAPK/ERK activation characterizes acquired resistance to EGFR-tyrosine kinase inhibitors in non-small cell lung cancer.Oncology letters · 2026Article
- The role of miR-335-5p in the redifferentiation of BRAF p.V600E thyroid cancers.Molecular oncology · 2026Article
- ADA assays for high-dose biologics: redefining drug tolerance through clinical insights.Bioanalysis · 2026Article
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundGastric cancer (GC) has always been a great threat to human health due to its aggressiveness and lethality. Anlotinib, a novel multi-target tyrosine kinase inhibitor (TKI), has been certified its anti-tumor effects on various tumors. Nonetheless, there are few studies on applying anlotinib as a treatment for GC. The underlying mechanism of acquired resistance during anlotinib administration remains unclear.
methodsWe investigated the toxicologic effects of anlotinib on GC cells through CCK8, colony-forming, and flow cytometry assays in vitro and xenograft models in vivo. Anlotinib-resistant GC cells, AGS-R and MGC803-R, were generated and characterized by cell proliferation and apoptosis assays. The signaling pathways involved in anlotinib resistance were probed using Cignal™ Finder 10-Pathway Reporter Array. Western blot and dual-luciferase reporter assays were performed to confirm the relationships. The TGF-β inhibitor LY364947 was introduced to demonstrate the importance of TGF-β signaling in anlotinib resistance via a series of functional assays.
resultsAnlotinib suppressed cell growth and induced apoptosis in vitro and inhibited tumorigenesis and metastasis in vivo, while its anti-tumor effects were impaired in anlotinib-resistant cells. The results of dual-luciferase reporter assays and western blot indicated TGF-β signaling was activated in anlotinib-resistant GC cells. LY364947 combined with Anlotinib exerted a better antineoplastic effect than monotherapy and considerably reversed the anlotinib resistance in GC.
conclusionsOur findings suggested that TGF-β signaling may take a significant part in anlotinib resistance in GC. The suppression of TGF-β signaling may be a possible and promising approach for the GC oncotherapy when combined with anlotinib.
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Registered trials
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