ArticleCancer chemotherapy and pharmacology2020
Notch1 and PI3K/Akt signaling blockers DAPT and LY294002 coordinately inhibit metastasis of gastric cancer through mutual enhancement.
Article in Cancer chemotherapy and pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 26 citations in OpenAlex.
- γ-Secretase inhibitor ameliorates thyroid autoimmune damage via blocking Notch1 signaling and reducing γδT17 cells in EAT mice.Endocrine journal · 2026Article
- Elucidating the Potential Targets and Mechanisms of Bisphenol A-Induced Prostate Cancer Based on Network Toxicology and Molecular Docking Analyses.Oncology research · 2026Article
- Emerging roles of Notch signaling in the tumor microenvironment of digestive system cancers.Frontiers in molecular biosciences · 2026Review
- Hes1 in malignant tumors: from molecular mechanism to therapeutic potential.Frontiers in immunology · 2025Review
- Notch signaling regulates Th17 cells differentiation through PI3K/AKT/mTORC1 pathway and involves in the thyroid injury of autoimmune thyroiditis.Journal of endocrinological investigation · 2024Article
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Atractylodin and β-eudesmol from Atractylodes lancea (Thunb.) DC. Inhibit Cholangiocarcinoma Cell Proliferation by Downregulating the Notch Signaling Pathway.Asian Pacific journal of cancer prevention : APJCP · 2023Article
- The TRPM4 channel inhibitor 9-phenanthrol alleviates cerebral edema after traumatic brain injury in rats.Frontiers in pharmacology · 2023Article
- Baicalein facilitates gastric cancer cell apoptosis by triggering endoplasmic reticulum stress via repression of the PI3K/AKT pathway.Applied biological chemistry · 2023Article
- Notch1/Hes1‑PTEN/AKT/IL‑17A feedback loop regulates Th17 cell differentiation in mouse psoriasis‑like skin inflammation.Molecular medicine reports · 2022Article
- Notch signaling in the pathogenesis, progression and identification of potential targets for cholangiocarcinoma (Review).Molecular and clinical oncology · 2022Review
- DAPT Attenuates Cadmium-Induced Toxicity in Mice by Inhibiting Inflammation and the Notch/HES-1 Signaling Axis.Frontiers in pharmacology · 2022Article
- Inhibiting Cytoprotective Autophagy in Cancer Therapy: An Update on Pharmacological Small-Molecule Compounds.Frontiers in pharmacology · 2022Review
- Identifying the Effect of COVID-19 Infection in Multiple Myeloma and Diffuse Large B-Cell Lymphoma Patients Using Bioinformatics and System Biology.Computational and mathematical methods in medicine · 2022Article
- A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database.Cancers · 2021Article
- Comprehensive understanding of anchorage-independent survival and its implication in cancer metastasis.Cell death & disease · 2021Review
- Tumor reversion: a dream or a reality.Biomarker research · 2021Review
- A Comprehensive Bioinformatic Analysis of NOTCH Pathway Involvement in Stomach Adenocarcinoma.Disease markers · 2021Article
- The biochemical and clinical implications of phosphatase and tensin homolog deleted on chromosome ten in different cancers.American journal of cancer research · 2021Review
- Thymosin‑β 4 induces angiogenesis in critical limb ischemia mice via regulating Notch/NF‑κB pathway.International journal of molecular medicine · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeBlockade of either Notch1 or PI3K/Akt pathway inhibits metastasis of gastric cancer. However, whether blockade of both pathways coordinately exerts such an effect remains unknown. In this study, we aimed to investigate the effects of combined treatment with Notch1 signaling blocker DAPT and PI3K/Akt signal blocker LY294002 on metastasis of gastric cancer.
methodsNotch intracellular domain (NICD) and phosphorylated Akt (p-Akt) levels in gastric cancer tissues and their adjacent normal tissue samples and gastric cancer SGC7901 and AGS cells and normal GES-1 cells were determined using immunohistochemistry and Western blotting. The effects of combined DAPT and LY294002 on metastasis of gastric cancer were evaluated by examining migration and invasion potential of SGC7901 cells using wound healing and transwell assays, determining changes in the levels of epithelial-mesenchymal transition biomarkers and MMP-9, Notch1, HES1, and phosphorylation of Akt in gastric cancer SGC7901 cells and/or AGS cells in vitro using Western blotting, and metastasis of gastric cancer to lungs in BALB/c nude mice after treatment.
resultsNICD and p-Akt levels were significantly higher in gastric cancer tissues and SGC7901 and AGS cells than those in the normal control and GES-1 cells. Migration and invasion potential of SGC7901 cells, EMT biomarkers and MMP-9 in SGC7901 cells, and metastasis of gastric cancer to lungs in mice were coordinately inhibited by DAPT and LY294002. In addition, DAPT and LY294002 coordinately inhibited the levels of Notch1, HES1, and p-Akt in gastric cancer cells.
conclusionDAPT and LY294002 coordinately inhibited metastasis of gastric cancer through mutual enhancement.
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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.