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

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

Content Provider	Scilit
Author	Shi, Ni Yu, Hao Chen, Tong
Copyright Year	2019
Description	Journal: OncoTargets and therapy 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.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756275/pdf https://www.dovepress.com/getfile.php?fileID=52796
Ending Page	7647
Page Count	11
Starting Page	7637
ISSN	11786930
DOI	10.2147/ott.s205457
Journal	OncoTargets and therapy
Volume Number	ume 12
Language	English
Publisher	Informa UK Limited
Publisher Date	2019-09-01
Access Restriction	Open
Subject Keyword	Journal: OncoTargets and therapy Esophageal Squamous Cell Carcinoma Pi3k/akt/mtor
Content Type	Text
Subject	Pharmacology (medical) Oncology

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