Dataset Information

Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.

ABSTRACT: Background:The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is implicated in several cancers. AKT allosteric inhibitor MK2206 and dual PI3K and mTOR inhibitor BEZ235 are promising drug candidates with potential anti-tumor effects. Purpose:In this study, we aimed to detect the activation of PI3K/AKT/mTOR pathway and assess the efficacy of MK2206 and BEZ235 in inhibiting esophageal cancer growth. Materials and methods:We used three different systems including carcinogen-induced animal model, human esophageal squamous cell carcinoma (SCC) cell lines, and xenograft mouse model. Results:Our data indicated that components of the PI3K/AKT/mTOR pathway were overexpressed and activated in esophageal SCC. MK2206 and BEZ235 inhibited cell proliferation, enhanced apoptosis, and induced cell-cycle arrest through downstream effectors SKP2, MCL-1, and cyclin D1 in esophageal SCC cells. MK2206 and BEZ235 also inhibited tumor growth in xenograft mice through the inhibition of AKT phosphorylation. MK2206/BEZ235 combination showed greater anti-tumor effect than MK2206 or BEZ235 alone. The enhanced efficacy of the combination was associated with the inhibition of phosphorylation ATK on both Thr308 and Ser473. Conclusion:The combination of MK2206 and BEZ235 exhibits potent antitumor effects and may have important clinical applications for esophageal SCC treatment.

SUBMITTER: Shi N

PROVIDER: S-EPMC6756275 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.

Shi Ni N Yu Hao H Chen Tong T

OncoTargets and therapy 20190917

<h4>Background</h4>The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is implicated in several cancers. AKT allosteric inhibitor MK2206 and dual PI3K and mTOR inhibitor BEZ235 are promising drug candidates with potential anti-tumor effects.<h4>Purpose</h4>In this study, we aimed to detect the activation of PI3K/AKT/mTOR pathway and assess the efficacy of MK2206 and BEZ235 in inhibiting esophageal cancer growth.<h4>Materials and methods</h ...[more]

PMID: 31571914

Similar Datasets

Project description:BackgroundGlobally, esophageal cancer ranks as the seventh most common cancer. Esophageal squamous cell carcinoma (ESCC) is one of its major histological types. ESCC accounts for the vast majority of cases in China, and the mortality rate is high. Cisplatin, the standard adjuvant chemotherapy drug for ESCC, has a modest response rate due to the development of drug resistance. Hinokiflavone (HF) is a natural biflavonoid compound with anti-melanoma activity. However, its anti-tumor effect on ESCC and the underlying mechanisms remain largely unknown.MethodsThe ESCC cell lines KYSE150 and TE14 were used. The cell counting kit-8 assay and flow cytometry analysis, along with colony formation, EdU, wound healing, and Transwell migration assays, were performed to assess cell characteristics (viability, migration, invasion, and apoptosis) following treatment with HF. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), western blotting, and molecular docking were used to investigate the pathways potentially modulated by HF. In vivo anti-tumor effects of HF were also investigated using a mouse xenograft model.ResultsOur findings revealed that HF inhibited ESCC cell proliferation. Hoechst 33342 staining, annexin V-FITC/PI staining, and western blotting confirmed that HF causes caspase-dependent apoptosis. KEGG pathway enrichment analysis and western blotting indicated that the PI3K/AKT/mTOR pathway played an important role in the process of HF-induced apoptosis. Furthermore, HF effectively impaired the migration and invasion abilities of KYSE150 cells and downregulated the expression of the matrix metalloproteinases (MMP) MMP2 and MMP9. HF inhibited tumor growth and exhibited minimal toxicity in the organs of the KYSE150 xenograft model.ConclusionThis is the first study to demonstrate the inhibition of ESCC growth and progression by HF. The underlying mechanism is through blocking the PI3K/AKT/mTOR signaling pathway, thereby inhibiting cell proliferation and inducing apoptosis. HF can be used as a complementary/alternative agent for ESCC therapy.

Dataset Information

Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.

Publications

Inhibition of esophageal cancer growth through the suppression of PI3K/AKT/mTOR signaling pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets