ArticleBioengineered2022
Synergistic anticancer effects of everolimus (RAD001) and Rhein on gastric cancer cells via phosphoinositide-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway.
Article in Bioengineered, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 18 citations in OpenAlex.
- Targeting the PI3K/AKT/mTOR pathway in gastrointestinal cancers: a comprehensive review of mechanisms, preclinical evidence, and clinical challenges.Medical oncology (Northwood, London, England) · 2026Review
- GLI3 is Inhibited by miR-143-3p and Attenuates Septic-induced Lung Injury and Inflammation by Targeting SFRP1.Combinatorial chemistry & high throughput screening · 2026Article
- Synergistic Interactions of Anthraquinones with Conventional Cancer Therapies.Combinatorial chemistry & high throughput screening · 2026Review
- KRT23 promotes proliferation invasion and metastasis of gastric cancer through epithelial-mesenchymal transition mediated by the PI3K/AKT/mTOR signaling pathway.Translational cancer research · 2025Article
- The role of lipid metabolic interactions in reshaping the tumor microenvironment.Acta biochimica et biophysica Sinica · 2025Article
- Lignin-Derived Oligomers as Promising mTOR Inhibitors: Insights from Dynamics Simulations.International journal of molecular sciences · 2025Article
- From Nature to Nanomedicine: Enhancing the Antitumor Efficacy of Rhein, Curcumin, and Resveratrol.Medicina (Kaunas, Lithuania) · 2025Review
- Lactylation: a novel driver of drug resistance in the tumor microenvironment.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer.International journal of molecular sciences · 2024Review
- Roles of Rictor alterations in gastrointestinal tumors (Review).Oncology reports · 2024Article
- Research Progress on the Synergistic Anti-Tumor Effect of Natural Anti-Tumor Components of Chinese Herbal Medicine Combined with Chemotherapy Drugs.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Recent Advances in Cellular Signaling Interplay between Redox Metabolism and Autophagy Modulation in Cancer: An Overview of Molecular Mechanisms and Therapeutic Interventions.Antioxidants (Basel, Switzerland) · 2023Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Everolimus (RAD001) is a mTOR inhibitor and is widely used for the treatment of gastric cancer (GC). Evidence suggests that Rhein has anticancer effect on GC. But the synergistic effect and mechanism of RAD001 and Rhein combination on GC is not clear. The current study aims to clarify the combination of RAD001 and Rhein in GC treatment. We found Rhein dose-dependently repressed MGC-803 cell viability (50% inhibition concentration (IC50) value = 94.26 μM). Rhein (80 μM) significantly suppressed GC cell proliferation and invasion. RAD001 dose-dependently repressed MGC-803 cells viability (IC50 value = 45.41 nM). The combination of Rhein and RAD001 repressed MGC-803 cells viability, invasion, and proliferation compared to the administration of Rhein or RAD001 alone. Protein levels of epithelial-mesenchymal transition (EMT)-related molecules E-cadherin, N-cadherin and Vimentin expressions were significantly affected by the combination of Rhein and RAD001. The combination of Rhein and RAD001 significantly facilitated cell apoptosis and up-regulated expressions of cell apoptosis and cycle-related protein p53, cyclin-dependent kinase 4 (CDK4) and cyclin D1 compared to the administration of Rhein or RAD001 alone. Moreover, the combination of Rhein and RAD001 repressed the expressions of phosphorylation-phosphoinositide-3-kinase (p-PI3K), p-protein kinase B (p-AKT) and p-mammalian target of rapamycin (p-mTOR). Finally, the combination of RAD001 and Rhein significantly decreased tumor weight and volume, suppressed the expressions of p-PI3K, p-Akt and p-mTOR, and repressed cell proliferation marker Ki-67 expression, which exerted synergistic cancer prevention in GC
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